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Biomedical subjects

D E Casey

Publications and source records attributed to D E Casey.

At least 55 records · Page 3Linked to original sources
PubMed1992

Underrecognition of tardive dyskinesia and drug-induced parkinsonism by psychiatric residents.

Recognition of tardive dyskinesia (TD) and other neuroleptic, drug-induced, extrapyramidal side effects presents a major challenge in modern clinical psychopharmacology. Failure to recognize these disorders can lead to poor patient care and may contribute to societal pressure for external control of psychiatric practice. This study reports the occurrence of tardive dyskinesia and drug-induced parkinsonism (DIP) in 101 inpatients, and documents underrecognition of both disorders by resident physicians. Researchers noted TD in 28% of cases and residents only described TD (or symptoms of TD) in 12%. The researcher determined DIP prevalence rate of 26% contrasted with an 11% rate found by residents. Patients with psychotic disorders were more likely than other patients to have researcher-identified TD, whereas DIP (researcher cases) occurred more often in patients with affective diagnoses. Residents tended to miss milder cases of TD, and to miss DIP in younger patients and in patients with affective disorders. Improved teaching and clinical exams are recommended to improve recognition.

Adult↗
PubMed1992

A longitudinal study of correlations among tardive dyskinesia, drug-induced parkinsonism, and psychosis.

Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) have been hypothesized to reflect opposing states of dopamine (DA) function. In this longitudinal study, 57 psychotic inpatients were rated repeatedly for TD, DIP, and psychosis while receiving neuroleptic medication. Cross-sectional correlations among TD, DIP, and psychosis were weak or nonexistent. Factor and cluster analyses found that 13 patients (23%) were classified into groups characterized by the expected negative correlations. Thus, only partial support was found for the hypothesis that TD and DIP represent opposing states of DA function.

Adult↗
PubMed1992

Tardive dyskinesia and diabetes mellitus.

Two studies examine the prevalence of tardive dyskinesia (TD) in neuroleptic-treated diabetic patients. Study 1 compared 38 diabetic patients with 38 nondiabetic patients treated for psychotic disorders with low to moderate doses of neuroleptics (mean chlorpromazine equivalents = 300 mg/day) for an average of 18 years. Study 2 compared 24 diabetic and 27 nondiabetic patients treated for an average of 2.6 years with a mean 31 mg/day of metoclopramide for gastrointestinal disease. Patients were examined for TD using standardized scales by raters blind to all treatment and illness variables. In both studies, there were no differences between the diabetic and nondiabetic groups in age, sex, type of psychiatric illness, and dose and duration of neuroleptic treatment or severity of parkinsonism. In both studies, the diabetic patients had significantly greater prevalence and severity of TD. No measures of diabetes severity were associated with TD in either study. Possible pathophysiologic mechanisms for the increased prevalence of TD in neuroleptic-treated patients with diabetes will be discussed.

Adult↗
PubMed1992

Coadministration of haloperidol and SCH-23390 prevents the increase in "perforated" synapses due to either drug alone.

Perforated synapses, which have a discontinuous density along the postsynaptic membrane, undergo changes in numbers under various experimental conditions. We have previously shown that 14-day administration of haloperidol, a typical neuroleptic which induces extrapyramidal side effects (EPS) and tardive dyskinesia (TD) in patients, causes an increase in the percentage of perforated synapses within the caudate nucleus. This increase was reversed if the animals were taken off the drug for an equal period of time (14 days). There was no effect within the nucleus accumbens. The atypical antipsychotic drug, clozapine, which when administered precipitates a very much lower incidence of EPS and TD, had no effect on the percentage of perforated synapses within either the caudate or nucleus accumbens. Because clozapine binds to both dopamine (DA) D1 and D2 receptors, it was of interest to determine if any changes in perforated synapses occurred following administration of the specific D1 antagonist, SCH-23390. Furthermore, because the action of D2 agonist may be dependent on the activation of the D1 receptor, we asked whether concomitant blockade of the D1 receptor could prevent the increase in perforated synapses due to the action of haloperidol, a drug which upregulates D2 receptors. We found that 14-day treatment with SCH-23390 (1.0 mg/kg per day) or haloperidol (0.5 mg/kg per day) caused an increase in the percentage of perforated synapses within the caudate but not the nucleus accumbens. There was a corresponding increase in DA D1 and D2 receptors in the caudate following administration of SCH-23390 or haloperidol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Three-year follow-up of older schizophrenics: extrapyramidal syndromes, psychiatric symptoms, and ventricular brain ratio.

Longitudinal evaluation of psychiatric patients often yields information that cross-sectional study does not. We previously examined 31 older (age greater than 55) chronic schizophrenics for prevalence of extrapyramidal side effects, severity of psychiatric symptoms, and ventricular brain ratio (VBR). We reexamined 22 of these patients after 2-4 years. Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) were common (mean prevalences were 52% and 62%, respectively) and often occurred together (38%). The overall prevalences of the disorders did not change significantly with time, although there was some individual fluctuation in diagnosis. Severity of TD was constant, but severity of DIP decreased, probably because neuroleptic doses were significantly decreased. Magnitude of DIP was positively correlated with VBR and severity of negative symptoms of schizophrenia. The correlation of DIP and negative symptoms occurred primarily because of the similarity between masked facies and blunted affect. VBR did not change over the follow-up period. Negative symptoms of schizophrenia were prevalent, moderately severe, and quite stable over time in this cohort. Positive symptoms were less severe but highly variable between examinations.

Antipsychotic Agents↗
PubMed1991

The prevalence of tardive dyskinesia in neuroleptic-treated diabetics. A controlled study.

In a controlled study, we compared the prevalence of tardive dyskinesia in 38 neuroleptic-treated diabetics with the prevalence of tardive dyskinesia in a group of 38 nondiabetic neuroleptic-treated controls, matched for age, sex, psychiatric diagnosis, and dose and duration of neuroleptic treatment. Members of each group were evaluated for movement disorders by a rater who used standard rating scales and was "blind" to all diagnoses and treatments. Neuroleptic-treated diabetics had a significantly higher prevalence and severity of tardive dyskinesia. There were no differences between groups on other possible risk factors for tardive dyskinesia, including parkinsonism, anticholinergic drug treatment, or cognitive function. These data suggest that diabetes mellitus should be examined further as a risk factor for tardive dyskinesia.

Age Factors↗
PubMed1991

Use of neuroleptic-induced extrapyramidal symptoms to predict future vulnerability to side effects.

OBJECTIVE: Susceptibility to neuroleptic-induced extrapyramidal syndromes varies widely, even within age and sex subgroups. Individual vulnerability to extrapyramidal syndromes has been assumed to explain this, but the utility of past history for predicting future occurrence of extrapyramidal syndromes has not been studied extensively. This investigation was undertaken to determine whether patients' previous histories of extrapyramidal syndromes predict future episodes of extrapyramidal syndromes and to compare the importance of this predictive factor with patient age, sex, neuroleptic dose, and anticholinergic dose as predictors of extrapyramidal syndromes. METHODS: The charts of 62 schizophrenic patients with multiple neuroleptic treatment episodes were reviewed. Extrapyramidal syndromes, neuroleptic drug doses, and anticholinergic drug doses during the first 21 days of each treatment episode were recorded. RESULTS: Previous extrapyramidal syndromes correctly predicted extrapyramidal syndromes in subsequent treatments for 84% of the patients. Variations in neuroleptic potency, neuroleptic dose, and anticholinergic dose partially explained incorrect predictions. CONCLUSIONS: These results support the hypothesis that patients with a history of extrapyramidal syndromes are at greater risk for future extrapyramidal syndromes. If confirmed, these results strongly support individual susceptibility as a major predictor of extrapyramidal syndromes and indicate that prophylaxis of extrapyramidal syndromes should be considered for patients who have previously suffered extrapyramidal syndromes from similarly prescribed neuroleptic therapy.

Adult↗
PubMed1991

Extrapyramidal syndromes in nonhuman primates: typical and atypical neuroleptics.

The traditional (typical) neuroleptic drugs produce acute extrapyramidal symptoms (EPS) in the majority of patients, whereas the atypical neuroleptics produce only minimal motor system side effects. Studies of acute dystonia in nonhuman primates with typical (haloperidol, fluphenazine), atypical (clozapine), and putative novel antipsychotic compounds with low EPS (remoxipride, melperone) were conducted across a wide dose range in double-blind, placebo-controlled trials. Haloperidol and fluphenazine caused dystonia, and clozapine did not. Remoxipride and melperone also produced dystonia, but remoxipride only did so at doses that were higher than needed for antipsychotic efficacy. Melperone produced dystonia in doses that are in the antipsychotic dose range. The clinical relevance of the findings is discussed.

Animals↗
PubMed1990

Remoxipride, a new selective D2 antagonist, and haloperidol in cebus monkeys.

1. Nine Cebus monkeys, 6 with mild spontaneous oral dyskinesia (tongue protrusions), were tested with two dopamine D2 antagonists, remoxipride (a new substituted benzamide) and haloperidol, and with two dopamine agonists, methylphenidate and apomorphine. 2. Remoxipride 4 and 8 mg/kg and haloperidol 0.01 and 0.02 mg/kg given alone induced identical dystonic-dyskinetic syndromes. 3. Methylphenidate 0.5 mg/kg caused increased arousal, but reduced oral dyskinesia, while apomorphine 0.25 mg/kg slightly increased arousal and induced/aggravated oral dyskinesia. 4. Remoxipride 2 and 4 mg/kg and haloperidol 0.005 and 0.01 mg/kg equally antagonized the methylphenidate- and apomorphine-induced arousal, but not oral dyskinesia. 5. Marked sedation was seen when apomorphine was given together with either D2 receptor antagonists. 6. It is concluded that remoxipride and haloperidol have a similar qualitative effect in motor behavior in Cebus monkeys, but the quantitative difference between the dystonia-inducing dose levels of the two drugs compared with the antipsychotic dose levels (estimated from clinical studies) suggests that remoxipride may cause relatively few extrapyramidal side-effects in human.

Animals↗
PubMed1990

Tardive dyskinesia.

Tardive dyskinesia is a potentially irreversible syndrome of involuntary hyperkinetic movements that occur in predisposed persons receiving extended neuroleptic (antipsychotic) drug therapy. It is usually characterized by choreoathetoid dyskinesias in the orofacial, limb, and truncal regions, but subtypes of this syndrome may include tardive dystonia and tardive akathisia. Although the mechanisms underlying the pathogenesis and pathophysiology of this disorder are unproven, altered dopaminergic functions will likely play a role in any explanation of it. Tardive dyskinesia develops in 20% of neuroleptic-treated patients, but high-risk groups such as the elderly have substantially higher rates. Risk factors include age, female sex, affective disorders, and probably those without psychotic diagnoses, including patients receiving drugs with antidopaminergic activity for nausea or gastrointestinal dysfunction for extended periods. Total drug exposure is positively correlated with tardive dyskinesia risk. Management strategies include a careful evaluation of both the psychiatric and neurologic states, a broad differential diagnosis, and adjustment of neuroleptic agents to the lowest effective dose that controls psychosis and minimizes motor side effects. No drug therapy is uniformly safe and effective for treating this disorder. A favorable long-term outcome of improvement or resolution correlates with younger age, early detection, lower drug exposure, and duration of follow-up.

Antipsychotic Agents↗
PubMed1989

Regional, reversible ultrastructural changes in rat brain with chronic neuroleptic treatment.

Administration of the dopamine receptor antagonist (neuroleptic, antipsychotic), haloperidol, resulting in an increase in the number of dopamine binding sites in the striatum and nucleus accumbens, has been well established. These increases disappear following withdrawal of treatment. Ultrastructurally, we found an increase in the number of synapses containing perforated postsynaptic densities (PSDs) following haloperidol administration within the caudate nucleus but not within the nucleus accumbens. The effect in the caudate reversed following cessation of treatment. We speculate that the terminals undergoing the change are not dopaminergic but may originate from the cerebral cortex. This reversible morphological increase associated with dopamine antagonist drug therapy may be reflective of the tolerance developed to neuroleptic drug-induced extrapyramidal syndromes and/or may be associated with abnormal motor movements of tardive dyskinesia that occur following long-term treatment.

Animals↗
PubMed1989

Clozapine: neuroleptic-induced EPS and tardive dyskinesia.

Clozapine has had a uniquely favorable motor system side effect profile since its initial evaluations. This has been convincingly corroborated by many double blind, single blind, and open studies treating acute and chronic psychosis. The acute extrapyramidal syndromes of dystonia, akathisia and parkinsonism infrequently occur, whereas these syndromes develop in up to 75% of patients receiving traditional neuroleptics. Tardive dyskinesia can be suppressed with higher doses of clozapine given over extended periods. However, an antipsychotic effect can be achieved in many patients at doses below the dyskinesia suppressing level. There is no established causative relationship between clozapine and tardive dyskinesia, but there is a theoretical basis that this may occur. Preliminary data suggest clozapine has mild antiparkinsonian effects as well as efficacy in controlling dopamine agonist-induced psychosis without aggravating parkinsonism. A much wider use of clozapine will further characterize the magnitude of differences compared to other neuroleptics, and identify additional indications for this special compound.

Basal Ganglia Diseases↗
PubMed1989

Lack of platelet monoamine oxidase activity in Cebus monkeys (Cebus albifrons).

1. Recent evidence suggests that monoamine oxidase (MAO) plays an important role modulating the extrapyramidal syndromes produced by neuroleptic drugs in both human and nonhuman primates. 2. To evaluate the possibility of using peripheral blood platelet MAO-B levels as indices of central nervous system MAO-B effects, we measured platelet MAO-B levels in Cebus monkeys that were previously tested with neuroleptics (N = 36) or drug naive (N = 6). 3. No platelet MAO-B was consistently detectable in these blood samples. 4. Thus platelet measures of MAO-B do not reliably reflect brain MAO-B function in nonhuman primates and do not offer a useful model for studying blood-brain MAO-B relationships.

Animals↗
PubMed1989

Serotonergic aspects of acute extrapyramidal syndromes in nonhuman primates.

Neuroleptic drug-induced acute extrapyramidal syndromes (EPS) are the major reasons why patients discontinue their antipsychotic medicines. Serotonin S2 antagonists prevent catalepsy in rodents but the effects in nonhuman primates have received only minimal study and deserve further evaluation as potential "non-neuroleptic neuroleptics" (antipsychotic effects free of acute EPS). Twenty Cebus monkeys (22 to 28 yrs. old) were tested with compounds that ranged from high to very low D2/S2 ratios. These were haloperidol, clopenthixol, tefludazine, and setoperone, all tested in the dosage range of .01 to .25 mg/kg and compared with saline i.m. once weekly in a random schedule. Dystonia was scored on four different symptoms by an experienced rater blind to drug dosage. All four active compounds produced clinically indistinguishable, dose related dystonia with very similar dose thresholds. In contrast to rodent studies these nonhuman primate investigations with drugs of widely differing D2/S2 antagonism ratios produced clinically similar EPS. Thus adding an S2 antagonism component to neuroleptics appears not to provide a unique approach to neuroleptic therapy which will be free of acute EPS.

Animals↗