A rating scale for extrapyramidal side effects
TL;DR: A modification of an earlier rating scale for extrapyramidal system disturbance is described, and evidence for the validity and reliability of the scale is presented.
Abstract: SUMMARY
A modification of an earlier rating scale for extrapyramidal system disturbance is described, and evidence for the validity and reliability of the scale is presented. The usefulness of the scale in studies of neuroleptic drugs is discussed. By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors.
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TL;DR: In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.
Abstract: • The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics.DSM-IIIschizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 ±14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the doubleblind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included "negative" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients.
3,842 citations
Journal Article•
TL;DR: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisio, and mild, moderate, and severe akath isia, and there is an item for rating global severity.
Abstract: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.
1,942 citations
TL;DR: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisias, and mild, moderate, and severe AKA as discussed by the authors.
Abstract: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.
1,927 citations
TL;DR: This finding indicates that neuroleptic-induced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia of drug-treated schizophrenic patients and demonstrates that clozapine is also "atypical" with respect to the central D1 occupancy in patients.
Abstract: • Positron emission tomography and selective radioligands were used to determine D,and D2dopamine receptor occupancy induced by neuroleptics in the basal ganglia of drug-treated schizophrenic patients. In 22 patients treated with conventional dosages of classical neuroleptics, the D2occupancy was 70% to 89%. Patients with acute extrapyramidal syndromes had a higher D2occupancy than those without side effects. This finding indicates that neurolepticinduced extrapyramidal syndromes are related to the degree of central D2occupancy induced in the basal ganglia. In five patients treated with clozapine, the prototype atypical antipsychotic drug, a lower D2occupancy of 38% to 63% was found. This finding demonstrates that clozapine is also "atypical" with respect to the central D2occupancy in patients. During treatment with clozapine, there is a low frequency of extrapyramidal syndromes, which accordingly may reflect the comparatively low D2occupancy induced by clinical doses of clozapine. Classical neuroleptics, like haloperidol or sulpiride, did not cause any evident D,occupancy, but the thioxanthene flupentixol induced a 36% to 44% occupancy. In four patients treated with clozapine, the D1occupancy was 38% to 52%. The D,occupancy induced by clozapine and flupentixol may contribute to the antipsychotic effect of these drugs.
1,357 citations
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TL;DR: The major portion of this monograph consists of a restatement by the senior author of his concepts regarding the modus operandi and therapeutic use of the neuroleptic drugs in clinical psychiatry.
Abstract: The title of this recent release is unfortunately misleading. There is here no real discussion of the pharmacology of the neuroleptic drugs and no reference to the extensive work of the past decade on their complex actions on the metabolism and function of the central and peripheral nervous system, liver, heart, and other organs. The major portion of this monograph (119 pages) consists of a restatement by the senior author of his concepts regarding the modus operandi and therapeutic use of the neuroleptic drugs in clinical psychiatry. One of the first investigators to work with reserpine, chlorpromazine, and related phenothiazines, Professor Haase has on several previous occasions indicated his view that the clinical efficacy of these drugs is intimately related to their extrapyramidal side effects, particularly the parkinsonian hypokinesia. He sees the latter as the motor expression of the decreased conation which he believes to represent the essential psychotherapeutic effect
1 citations