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Biomedical subjects

D E Casey

Publications and source records attributed to D E Casey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Movements in never-medicated schizophrenics: a preliminary study.

Descriptions of schizophrenia dating to the beginning of this century include mention of abnormal movements which are similar to tardive dyskinesia (TD), currently thought to be sequelae of neuroleptic medication. In order to examine the extent to which such movements might appear in the normal course of schizophrenia, we examined a sample of 22 never-medicated DSM-III-R schizophrenics who presented for treatment at a psychiatric center in Casablanca, Morocco. Duration of illness in this sample ranged from 1 to 10 years. Patients were assessed for choreoathetoid movements using the Abnormal Involuntary Movement Scale (AIMS). Videotaped and live examinations were rated by the investigators. Three patients (14%) met research diagnostic criteria for probable SD. Mild movements in one body part (AIMS = 2) were seen in an additional five (23%) patients. The movements were characteristic of TD, although their somatic distribution differed from previous studies. Total AIMS score increased with age and duration of illness (r = 0.64, P < 0.01). These findings suggest that choreoathetoid movements may appear spontaneously in patients with schizophrenia.

Adolescent↗
PubMed1996

Side effect profiles of new antipsychotic agents.

Although neuroleptic drugs have become the mainstay of treating acute and chronic psychosis, they are substantially limited by troublesome side effects. The traditional neuroleptic drugs have a wide array of central nervous system and peripheral system side effects that often lead to problems in management or patient noncompliance. Of particular difficulty are the extrapyramidal symptoms and tardive dyskinesia. However, other side effects of seizures, sedation, neuroleptic malignant syndrome and cardiovascular, hematologic, endocrinological, and weight gain problems remain as clinical management challenges posed by existing antipsychotic drug therapy. Considerable progress has been made in improving the motor side effect profile with the advent of clozapine and risperidone. However, each of these drugs has its own dose-limiting side effect profile. Two new drugs, olanzapine and sertindole, are now added to the pharmacopeia for treating psychosis. They further improve the benefit/ risk ratio because they have even fewer EPS and other side effects. Overall, these new antipsychotic agents greatly improve the treatment of psychosis by reducing drug-induced morbidity and improving the quality of life for patients.

Antipsychotic Agents↗
PubMed1995

The effects of D1 (NNC 22-0215) and D2 (haloperidol) antagonists in a chronic double-blind placebo controlled trial in cebus monkeys.

The effects of chronic treatment for 28 days with the oral D1 (NNC 22-0215) or D2 (haloperidol) antagonist were evaluated in nonhuman primates in a double blind, placebo controlled crossover trial. Cebus monkeys, 10-18 years old, which were previously sensitized to neuroleptics, were treated in three different groups with NNC 22-0215 2-3 mg/kg PO (n = 6), haloperidol 2-3 mg/kg PO (n = 5), or lactose placebo (n = 7) each day in a banana slice. At the end of 28 days the NNC 22-0215 group crossed over to haloperidol and the haloperidol group crossed over to NNC 22-0215 for 28 more days. The lactose group continued on lactose. Extrapyramidal symptoms (EPS) of dystonia and sedation were scored daily. Initially both NNC 22-0215 and haloperidol produced equal rates of dystonia. However, the NNC 22-0215 group demonstrated nearly full desensitization by day 2 and showed no EPS by day 6, whereas the haloperidol group had increased EPS during the first week, followed by moderate desensitization to EPS, but continued to have symptoms on each of the 28 days of treatment. At crossover, the previously treated haloperidol group rapidly desensitized with NNC 22-0215 by day 4 to show no EPS, whereas the previously treated NNC 22-0215 group showed full EPS on the first day of haloperidol and had EPS continue over the next 28 days of treatment. Sedation from NNC 22-0215 also desensitized within the first week of treatment. Haloperidol produced minimal sedation that did not change. The profound difference in rates of desensitization between repeated D1 and D2 antagonist treatment suggests that D1 antagonists in the clinic may produce EPS side effects for only the first few days, in contrast to the continuous acute EPS associated with chronic neuroleptic treatment.

Administration, Oral↗
PubMed1995

Motor and mental aspects of extrapyramidal syndromes.

Neuroleptic-induced extrapyramidal syndromes (EPS) are major limitations to effective antipsychotic therapy. There are both motor (objective) and mental (subjective) components to EPS, which must be considered in the evaluation and differential diagnosis of treatment-related adverse events. In addition to causing motor impairment, these syndromes can also produce irritability, anxiousness and secondary negative symptoms of slow thinking and emotional blunting. The EPS of akathisia, dystonia, and parkinsonism have unique characteristics that are influenced by patient, drug and temporal aspects. With the advent of new and novel antipsychotic drugs that have low EPS liability, patients will have fewer side effects, be less non-compliant and more able to benefit from rehabilitation efforts.

Antipsychotic Agents↗
PubMed1994

Motor and mental aspects of acute extrapyramidal syndromes.

Acute extrapyramidal syndromes (EPS) are one of the major limitations to effective neuroleptic treatment. These disorders have both motor (objective) and mental (subjective) aspects, which must be considered in any evaluation and differential diagnosis of treatment-related side effects. The disorders of akathisia, acute dystonia and parkinsonism have unique features that are best understood in the context of a careful assessment of patient characteristics, drug factors and temporal aspects. Though acute EPS are commonly explained on the basis of dopamine D2 receptor antagonism, data from several lines of study raise important questions about this hypothesis. The roles of receptor subtype specificity, brain region selectivity and ratios of different receptor subtype antagonism are discussed. New and novel antipsychotic drugs with low rates of EPS are important clinical advancements that will increase patients' ability to participate in therapy and rehabilitation and thus improve their quality of life.

Akathisia, Drug-Induced↗
PubMed1994

Ten-year outcome of tardive dyskinesia.

OBJECTIVE: The purpose of this study was to assess the long-term outcome of patients with tardive dyskinesia. METHOD: A group of 122 neuroleptic-treated Hungarian outpatients were assessed for tardive dyskinesia on the Abnormal Involuntary Movement Scale and the Tardive Dyskinesia Rating Scale by the same rater over a 10-year period. RESULTS: Sixty-three of the patients received both 5- and 10-year follow-up assessments and are the subjects of this report. The overall prevalence of tardive dyskinesia in this group changed little over time; it was 30.2% at baseline, 36.5% at 5 years, and 31.7% at 10 years. However, there were changes in the tardive dyskinesia status of individual patients; 11 patients had remissions, and 12 who did not have tardive dyskinesia at the baseline assessment had developed it by the 10-year assessment. These two subgroups did not differ significantly on demographic and drug history variables. Outcome of tardive dyskinesia was not significantly related to neuroleptic treatment or to age. CONCLUSIONS: The data of this 10-year follow-up study provide evidence for the long-term stability of tardive dyskinesia and for the feasibility of maintenance neuroleptic therapy for chronic psychotic patients who have tardive dyskinesia.

Adult↗
PubMed1994

Striking a balance between safety and efficacy: experience with the SSRI sertraline.

Depression is a widespread and serious disorder inflicting an immeasurable toll on the lives of millions of people and affecting their families and colleagues. It is the cause of countless suicides especially in those whose illness has not been detected or given appropriate care. Until recently, effective pharmacotherapeutic management of depression was hampered by the troublesome side effects associated with traditional methods of treatment. In an attempt to circumvent these adverse effects, many antidepressants were prescribed at less than therapeutic doses, resulting in a high probability of inadequate treatment, relapse, or recurrence. The development of the selective serotonin reuptake inhibitors (SSRIs) was guided by the need for an antidepressant that provided both safe and effective therapeutic benefit. Sertraline's potent and highly selective inhibition of serotonin accounts both for its efficacy in a broad spectrum of depression and for its high tolerability and ease of use. Its safety and tolerability have been demonstrated in acute and maintenance phases of treatment and establishes that sertraline provides a viable clinical alternative for acute and long-term care of depressed patients.

1-Naphthylamine↗
PubMed1993

The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders.

BACKGROUND: Metoclopramide hydrochloride, a neuroleptic dopamine receptor antagonist used to treat gastric ailments, is reported to cause extrapyramidal movement disorders. The goals of this study were (1) to determine the prevalence and severity of tardive dyskinesia and acute extrapyramidal movement syndromes including akathisia, acute dystonia, and drug-induced parkinsonism in metoclopramide-treated patients and (2) to compare the prevalence and severity of tardive dyskinesia in metoclopramide-treated diabetics and nondiabetics. METHODS: From a list of metoclopramide-treated patients received from the Portland (Ore) Veterans Affairs Medical Center pharmacy, 53 patients met inclusion criteria and 51 (96%) agreed to participate. Controls consisted of a convenience sample drawn from the Portland Veterans Affairs Medical Center Outpatient Clinic who were matched to subjects on age (+/- 10 years), gender, and presence or absence of diabetes. Of 61 potential controls contacted, 51 (84%) agreed to participate. Metoclopramide-treated subjects and controls were seen by a rater who was "blind" to all diagnoses and treatments. The rater performed a standardized examination used to elicit signs and symptoms of tardive dyskinesia and acute extrapyramidal movement syndromes. RESULTS: The relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93 to 2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5 to 10.5). Metoclopramide-treated patients had significantly greater severity of tardive dyskinesia, drug-induced parkinsonism, and subjective akathisia than controls. Use of metoclopramide was associated with impairment in ambulation and increased use of benzodiazepines. Metoclopramide-treated diabetics had significantly greater severity of tardive dyskinesia than metoclopramide-treated nondiabetics. CONCLUSIONS: Metoclopramide use is associated with a significantly increased prevalence and severity of several extrapyramidal movement disorders.

Adult↗
PubMed1993

Serotonergic and dopaminergic aspects of neuroleptic-induced extrapyramidal syndromes in nonhuman primates.

Neuroleptic drug-induced acute extra-pyramidal syndromes are one of the major reasons why patients discontinue their antipsychotic medicines. The typical (e.g., haloperidol) neuroleptic drug produces acute extrapyramidal symptoms in the majority of patients, whereas the atypical (clozapine) neuroleptic produces only minimal motor system side effects. Serotonin S2 antagonists often reduce or prevent catalepsy in rodents, but the limited number of studies in nonhuman primates have produced conflicting results. The hypothesis of a high serotonin S2/dopamine D2 antagonism ratio as a mechanism underlying atypical neuroleptic effects in preventing acute extrapyramidal syndromes deserves further evaluation in nonhuman primate models because extrapyramidal symptoms in monkeys closely resemble those in patients. Cebus monkeys (22-28 years old) were tested with compounds that ranged from low to high S2/D2 antagonism ratios. These were haloperidol, fluphenazine, clopenthixol, melperone, tefludazine, setoperone, risperidone, and clozapine. A saline control was included with a wide dose range of each of these drugs that was tested in a once-weekly, blindly-scored random drug administration schedule. Dystonia was scored on four different symptoms by an experienced rater who was blind to drug dosage. All the compounds, with the exception of clozapine, produced clinically indistinguishable dose-related dystonia. The only difference was the dose at which dystonia appeared. In contrast to rodent studies, these nonhuman primate investigations with drugs, spanning a wide range of S2/D2 antagonism ratios, produced clinically similar extrapyramidal symptoms. Thus, adding an S2 antagonism component to neuroleptics does not appear to provide an explanation for the motor side effect profile of atypical neuroleptics, or a method for designing neuroleptic drugs that will be free of extrapyramidal symptoms.

Animals↗
PubMed1993

The St. Hans Rating Scale for extrapyramidal syndromes: reliability and validity.

The St. Hans Rating Scale (SHRS) is a multidimensional rating scale for the evaluation of neuroleptic-induced hyperkinesia, parkinsonism, akathisia and dystonia. This scale and the Abnormal Involuntary Movement Scale (AIMS) were tested by 7 raters (2 experienced, 2 less experienced and 3 totally inexperienced) in 30 psychiatric patients with tardive dyskinesia (TD). The test was performed 3 times in the same patients: 1) live evaluation during a video recording, 2) evaluation 2 weeks later from the videotape, and 3) evaluation after another 2 weeks from the same videotape. The intrarater reliability was high in the experienced group (0.91-0.96 for SHRS hyperkinesia scale, 0.80-0.84 for AIMS, and 0.82-0.97 for SHRS total parkinsonism). No significant changes occurred from live to video evaluation. The interrater reliability coefficient for the experienced group was also high: 0.89-0.95 for the SHRS hyperkinesia scale, 0.76-0.85 for the AIMS scale and 0.95-0.98 for the SHRS parkinsonism scale. The less experienced and the inexperienced raters had coefficients for intra- and interrater reliability that were 0.10 and 0.20 lower, respectively. The SHRS parkinsonism scale had a high construct validity, as determined by the homogeneity coefficients of Cronbach (0.82) and Loevinger (0.43). The corresponding coefficients for the hyperkinesia scales were low, in agreement with the individual distribution of TD (only about 50% present extremity dyskinesia and less than 25% facial, head and trunk dyskinesia, independent of the severity of the syndrome). Finally, convergent validity was found between the SHRS hyperkinesia scale and AIMS and divergent validity between all of the other scales.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Dose response of prophylactic antipsychotics.

A review of the literature concerning the use of oral and depot antipsychotic medication has high-lighted some important considerations in the treatment of chronic schizophrenic patients. All patients not treated with any form of antipsychotic drug will relapse within 3 years. These relapses will be more clinically significant and will occur at greater frequency than in patients who receive medication on a regular basis. Careful consideration should be given to each patient when choosing between oral or depot medication and inpatient or outpatient therapy. In addition, the clinician should consider the dosage schedule of each medication and balance this against the probability of extrapyramidal side effects and noncompliance. One option for the prevention of relapse without an increase in adverse side effects is the administration of depot haloperidol. For all therapeutic options, medication should be given on a regular basis, since intermittent dosing strategies do not work, and psychosocial rehabilitation should be initiated.

Administration, Oral↗
PubMed1993

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.

Adult↗
PubMed1992

Dopamine D1 (SCH 23390) and D2 (haloperidol) antagonists in drug-naive monkeys.

The ability of dopamine D1 antagonists to produce acute extrapyramidal syndromes (EPS) in nonhuman primates is unclear. Some studies in monkeys show that D1 antagonists produce acute dystonia, whereas other studies do not report these effects. The central issues that have yielded conflicting results revolve around prior treatment status (neuroleptic-naive versus neuroleptic sensitized) and route of administration (oral versus parenteral). In this study, separate groups of neuroleptic drug-naive cebus monkeys were tested once weekly with intramuscularly administered SCH 23390, a D1 antagonist, or haloperidol, a D2 antagonist, across a dose range of 0.01-0.25 mg/kg, and a saline control. Both active drugs, but not saline, produced clinically identical syndromes of acute dystonia and bradykinesia, though haloperidol induced higher symptom scores over a longer duration. Sedation and locomotor activity were unchanged by SCH 23390, but decreased with haloperidol. Factors regarding acute EPS liability in nonhuman primate models and clinical implications in man are discussed.

Animals↗
PubMed1992

Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex.

Perforated synapses, which contain a discontinuous density along the postsynaptic membrane, can increase or decrease in numbers following various behavioral and biochemical manipulations. We have previously established that 14-day treatment with haloperidol causes an increase in the number of perforated synapses within the caudate nucleus (dorsolateral region) but not the nucleus accumbens (Meshul and Casey 1989). This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time. We have now further examined the effects of haloperidol administration, which is associated with a high incidence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD), and assessed the effects of clozapine, which appears to have a lower potential for inducing EPS and TD. Administration of haloperidol for 2 weeks significantly increased the percentage of perforated synapses in the caudate, but not in the nucleus accumbens or layer VI of medial prefrontal cortex (MPCx). There was an increase in specific [125I]epidepride binding to D-2 receptors in the caudate nucleus and MPCx following haloperidol. Administration of clozapine for 2 weeks did not affect the percentage of perforated synapses in any of the three dopamine (DA)-rich regions that were examined. There was an increase in specific [3H]SCH 23390 binding to D-1 receptors and in specific [125I]epidepride binding to D-2 receptors only within MPCx following clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗