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Biomedical subjects

D E Casey

Publications and source records attributed to D E Casey.

At least 73 records · Page 4Linked to original sources
PubMed1988

Neuroleptic side effects: acute extrapyramidal syndromes and tardive dyskinesia.

The neuroleptic-induced motor system side effects of acute extrapyramidal syndromes (EPS) and tardive dyskinesia (TD) are the major limitations of these drugs. Effective strategies for managing these problems are based on the clinical presentations, pathophysiological processes, and a complex interaction of patient and treatment variables. New concepts about the causes and long-term outcome of acute EPS and TD are emerging to challenge some of the commonly held views about these syndromes. The primary method of preventing undue side effects is to use the lowest effective dose of both neuroleptic and anti-EPS drugs. The pressing need is for novel compounds which treat schizophrenia and are free of the undesirable motor system effects (a nonneuroleptic neuroleptic).

Antipsychotic Agents↗
PubMed1988

Seven-year follow-up of tardive dyskinesia in Hungarian outpatients.

Of 122 Hungarian outpatients treated with neuroleptics, 79 (64.8%) were available for follow-up 7 years after their original assessment for tardive dyskinesia (TD). Ratings on the Abnormal Involuntary Movements Scale and the Simpson Dyskinesia Rating Scale increased significantly. The number of TD cases identified by research diagnostic criteria increased by only 9%: 12 of 28 patients no longer showed TD 7 years later, while 19 of 51 patients developed new TD.

Adult↗
PubMed1988

Tardive dyskinesia.

Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression.

Adult↗
PubMed1988

Risk factors for drug-induced parkinsonism in tardive dyskinesia patients.

Using multivariate statistical analyses, the authors identified risk factors for development of drug-induced parkinsonism (DIP) in 66 tardive dyskinesia (TD) patients. Older age, recent use of neuroleptics, shorter duration of past neuroleptic exposure, and severity of TD were associated with increased risk of DIP. The clinician should devise treatment strategies in anticipation of the occurrence of DIP regardless of the presence or absence of TD, especially in older patients. New models for the pathophysiology of the two disorders are needed.

Adult↗
PubMed1988

Affective disorders and tardive dyskinesia.

Evidence from multiple lines of study indicate that mood disorders, particularly depression, are a risk factor for developing tardive dyskinesia (TD). Important patient and treatment factors include: 1) frequent retrospective rediagnosis of affective disorders instead of schizophrenia when the long-term course of illness and response is evaluated, and 2) TD onset after relatively brief (few months to few years) exposure to low to moderate neuroleptic doses. Mechanisms underlying this increased sensitivity to TD are unknown. It has been hypothesized that the cyclic mono- and catecholamine activity during mood changes makes the brain more vulnerable to the direct neuroleptic effects or the compensatory processes initiated by these drugs. There may also be an interaction between neuroleptic drugs and antidepressant agents which produce greater vulnerability to TD. Additionally, neuroleptic drug use may be different in affective disorders, such as high doses for short time periods with mania. Treating TD in patients with mood disorders is often difficult. The psychiatric diagnosis should be the first priority in treatment regimens. Then, strategies for addressing TD should be considered. Occasionally lithium and/or antidepressants may be effective in treating both affective disorders and TD in some patients. Specific drug therapies for TD have not been consistently effective. Therefore, the passage of time may be the best treatment approach. Preventing TD should receive the highest priority. In the short term, neuroleptic drugs should be limited to managing acute psychotic symptoms in patients with mood disorders. In the long term, neuroleptics should be reserved for manic or depressive symptoms that do not respond to standard therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipsychotic Agents↗
PubMed1987

Pargyline reduces/prevents neuroleptic-induced acute dystonia in monkeys.

The neuropharmacologic mechanisms underlying neuroleptic-induced extrapyramidal syndromes (EPS) were studied using a nonhuman primate model. Twenty-six Cebus albifrons monkeys were given weekly challenges of haloperidol (0.025 mg/kg IM), and half of the animals received the monoamine oxidase (MAO) inhibitor pargyline (5 mg/kg PO) daily for 17 consecutive days during the protocol. Pargyline caused no changes in baseline behaviors, but significantly reduced haloperidol-induced acute dystonia (AD) (-67%, P less than 0.002) and parkinsonism (-56%, P less than 0.005). The majority (8 of 13) of the experimental group had complete prevention of neuroleptic-induced EPS during cotreatment with pargyline. Behavioral scores returned to baseline levels after stopping pargyline, and did not show the further sensitization to haloperidol-induced AD that occurred in the control group. The possible mechanisms by which an MAO inhibitor might influence neuroleptic-induced AD were considered. The most likely explanation would appear to involve facilitation of striatal dopamine (DA) neurotransmission by inhibition of intra- and extraneuronal MAO, thus supporting the hypothesis that AD is due to decreased striatal DA function with secondary cholinergic hyperfunction.

Animals↗
PubMed1987

Neuroleptic-induced parkinsonism in older schizophrenics.

The association of neuroleptic drug-induced parkinsonism (DIP) with factors related to brain structure and function are poorly understood. Twenty-one medicated schizophrenics over age 55 years were evaluated for parkinsonism, tardive dyskinesia, psychiatric symptoms, ventricular/brain ratio (VBR), and neuropsychological function. Sixteen (76%) of the patients had DIP, whereas 10 (48%) had tardive dyskinesia. Increased severity of parkinsonism was significantly associated with larger VBR and the severity of negative symptoms. Severity of parkinsonism predicted poor visual-spatial function, whereas negative symptoms were modestly predictive of impairment in both verbal ability and cognitive flexibility. These findings suggest that brain atrophy may be a risk factor for DIP. The pattern of cognitive dysfunction associated with DIP in this sample is similar to that found in idiopathic Parkinson's disease. Dopaminergic dysfunction may underlie the pattern of pathology described in this report.

Aged↗
PubMed1987

Prediction of neuroleptic-induced dystonia.

For patients receiving neuroleptics, age, sex, neuroleptic potency, and dose all influence the likelihood of a dystonic reaction. Little is known, however, of the relative importance of these factors or of the feasibility of predicting dystonia in individual patients. We reviewed 135 charts of psychotic inpatients to examine these factors and their usefulness in predicting dystonia. Age, sex, neuroleptic type, dose, and occurrence of dystonia were recorded for the first 4 days of drug treatment and were used to construct a linear discriminant function that classified the cases as to whether dystonia was expected. Internal cross-validation was performed, and the error rate of this classification procedure was calculated. Forty-nine (36%) of the patients had dystonia. A younger age was the most powerful predictor of dystonia. Male gender was second in predictive power with minor effects from neuroleptic dose and potency. The overall error rate (false-positive and false-negative errors combined) of the discriminant function was 30%. These results suggest the possibility of predicting dystonia in individual patients but should be regarded with caution since the predictive procedure has not been tested prospectively. If confirmed, these data may allow treatment strategies that protect patients from dystonia while sparing patients not at risk unnecessary treatment with antiparkinson agents.

Adolescent↗
PubMed1985

Tardive dyskinesia in the aged. Duration of treatment relationships.

Although tardive dyskinesia (TD) is recognized to result from neuroleptic drug exposure, data conflict about the importance of the quantity of that exposure in producing TD. The relationship between duration of neuroleptic treatment (one to 301 months) and TD was studied in 57 elderly psychiatric inpatients. Examinations for TD and parkinsonism were quantified on the Abnormal Involuntary Movement Scale (AIMS) and on a parkinsonism severity scale. Prevalence of presumed TD was 49% and of parkinsonism 51%. Prevalence of TD increased with longer treatment, but parkinsonism was independent of treatment duration. Linear multiple regression analysis showed that the AIMS score was correlated positively with treatment duration and negatively with parkinsonism. Logistic multiple regression analysis verified these relationships and was more successful at predicting TD. The length of neuroleptic treatment necessary to produce TD was calculated from the logistic model at 10.8 months (95% confidence interval, zero to 25.6 months). These analyses showed the greatest rise in risk of TD occurred within the first two years of drug therapy.

Age Factors↗
PubMed1985

Tardive dyskinesia: reversible and irreversible.

The long-term prognosis of tardive dyskinesia (TD) has been insufficiently studied. Symptoms are reversible in many patients, but an irreversible course is widely believed to be the expected outcome. This pessimistic view has led to the assumption that neuroleptics should not be used in patients with TD because these drugs will produce an inevitable aggravation of TD. To clarify this issue, 27 patients were serially evaluated over 5 years for changes in neuroleptic treatment, TD, and mental status. Ten patients were able to discontinue medications; 15 required continued low-dose neuroleptic therapy [average 223 mg/day chlorpromazine (CPZ) equivalents], and two needed high doses (1000-2000 mg/day CPZ equivalents) to control psychosis. The majority of patients improved by more than 50% in both treated and untreated groups. In 8 of 27 patients (29.6%) TD resolved; in 1 patient TD increased by 25%. Younger patients improved the most. Prognosis was most favorable if neuroleptics were discontinued, but improvement was still possible with low to moderate doses (less than 600 mg/day CPZ equivalents). The large majority of patients with schizophrenia or schizoaffective illness relapsed, and required continued drug treatment. TD must be evaluated over several years to monitor the resolving/persisting course. Control of psychosis and improvement of TD during low-dose neuroleptic treatment suggest the antipsychotic and neurological effects of neuroleptics may involve different thresholds or mechanisms of action.

Adult↗
PubMed1985

Tardive dyskinesia: nondopaminergic treatment approaches.

The continuing concern about tardive dyskinesia (TD) has stimulated a broad search for therapies for this disorder. Since neuroleptic drugs are thought to be the etiological agents, acting presumably through dopamine receptor blockade, nondopaminergic drugs have been the focus of recent study. However, no uniformly safe and effective drug treatment has been identified. Augmentation of cholinergic function is theoretically attractive, but further research is needed to develop practical and effective compounds. GABA drugs do not consistently suppress TD. The effect of benzodiazepines in TD is unclear, but these agents may be of some temporary benefit in patients with distressing symptoms. Lithium, serotonergic compounds, and numerous neuropeptides all fail to have any consistent effect in TD. Early reports of benefit with alpha- and beta-noradrenergic agents are interesting but require further study. Many other drug types have been tried without benefit. For the majority of patients, it may be best to give no drug treatment. Any drug that is capable of suppressing TD may aggravate the disorder in the long term. The potential for a spontaneous gradual remission of TD is an argument in favor of a patient, nonaggressive, and cautiously optimistic approach to this disorder.

Basal Ganglia↗
PubMed1985

Behavioral effects of long-term neuroleptic treatment in Cebus monkeys.

Tardive dyskinesia (TD) occurs in predisposed individuals receiving neuroleptic treatment, but prior to the onset of symptoms it is not possible to predict who is at risk for this disorder. If the time course for evolving symptoms, perhaps mediated through dopamine hypersensitivity, could be identified, treatment interventions could be initiated. Eight male Cebus monkeys (15-18 years old) were tested with the dopamine agonists apomorphine, d-amphetamine, bromocriptine, and pergolide before, during, and after 3 months of treatment with haloperidol 0.25 mg/kg daily PO. This treatment cycle was repeated four times. Apomorphine and amphetamine produced moderate buccolinguo-masticatory (BLM) signs. Bromocriptine and pergolide produced very few BLMs. Initially haloperidol suppressed dopamine agonist-induced BLMs, but tolerance to the effect developed and was replaced by a potentiation of apomorphine-induced BLMs. Markedly increased apomorphine- and amphetamine-induced BLMs were seen following the first 3 months of haloperidol medication (behavioral hypersensitivity), but this gradually decreased to near-baseline levels, even with re-exposure to neuroleptics in the four treatment cycles. Bromocriptine and pergolide produced no signs of BLM behavioral hypersensitivity. These findings suggest that long-term neuroleptic treatment in nonhuman primates induces dynamic compensatory CNS changes, which may not fully explain the pathogenesis of TD on the basis of dopamine hypersensitivity.

Animals↗