Biomedical subjects
Publications and source records attributed to G Yagi.
We examined mortality rates (MR) during 10 years between schizophrenic inpatients with and without tardive dyskinesia (TD). The TD group had a significantly higher MR (41%), as compared with the control group (20%). However, we could not reveal critical factors to explain why the TD patients had the higher MR.
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We describe automated column-switching high-performance liquid chromatography for determining nine tricyclic and tetracyclic antidepressants (TCAs) and their metabolites in human serum. TSKgel ODS-80TM and TSKprecolumn PW (Tosoh Co., Tokyo) are used in the analytical column and the precolumn, respectively. A 200-microL serum sample is directly injected onto the precolumn. After washing the serum proteins from the precolumn with potassium phosphate buffer, the precolumn connection is switched to introduce the retained substances onto the analytical column. The drugs are then eluted within 30 min with an acetonitrile/potassium phosphate buffer mixture containing sodium 1-heptanesulfonate. The analytical recoveries (95-104%), reproducibilities (within-run CV less than 3%), and detection limits (10 micrograms/L) indicate that this HPLC system is suited for therapeutic drug monitoring. Correlations were good between the TCA concentrations in serum and administered dose (r = 0.713, n = 41), and between 10-hydroxynortriptyline and nortriptyline in serum (r = 0.691, n = 24).
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The authors followed the course of 11 patients with potentially reversible tardive dyskinesia while they were taking minimum effective neuroleptic doses. After 10 years, the symptoms of tardive dyskinesia had disappeared in eight patients, were minimal or questionable in one, and had become persistent in two.
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Haloperidol serum levels were determined by the recently developed radioimmunoassay technique to elucidate the relationship between serum levels and clinical effects and that between serum levels and adverse effects. The serum levels of haloperidol in divided daily doses schedule reached to the steady state more rapidly (within 7 days) than in single dose schedule. The single daily dose schedule showed significantly wider diurnal variation than the divided daily doses schedule. No remarkable differences in serum concentration was noted between different types of oral haloperidol preparation (liquid, granule, tablet). No definite relationship was established between the serum concentration of haloperidol and incidence of tardive dyskinesia. No definite positive relationship between clinical effects and serum concentration of haloperidol could obtained.
Haloperidol blood levels in patients were determined to elucidate the relationship between blood levels and clinical effects. Determinations of haloperidol serum were performed by radioimmunoassay and the clinical status was estimated using BPRS. The relationship between haloperidol serum levels and BPRS total score was studied in 20 chronic schizophrenics currently receiving haloperidol treatment. The results did not show positive relationship between these two. Another 11 schizophrenic patients were treated with daily doses of average 6 mg of haloperidol. The patients were classified into improved and unchanged group according to the changes of BPRS total score. All 7 cases classified into the improved group had short duration of the illness less than one year. In this group, the levels were lower initially but gradually rised in paralled with the increase of extent of recovery on BPRS. Furthermore, improvement of psychopathology by means of decrease of BPRS total score was still found after haloperidol serum levels reached a plateau. The results did not support the view that high blood concentration of haloperidol might contribute to the clinical effects, but still suggested utility of measuring blood levels in acute or subacute patients being treated with haloperidol medications.
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A radioimmunoassay has been developed which enables accurate determination of haloperidol in human serum. Antiserum was prepared by immunizing guinea pigs with haloperidol (O-carboxymethyl)oxime derivative (III) coupled with bovine serum albumin. With the antiserum, 3H-haloperidol and dextran-coated charcoal, the assay of haloperidol in serum was possible over a concentration range of 1 to 50 ng/ml, using 0.1 ml of human serum without the need of an extraction procedure. Data obtained by radioimmunoassay are in good agreement with those obtained by gas chromatography. No appreciable cross-reactivity was observed neither with haloperidol metabolites nor with other butyrophenone neuroleptics. Serum levels of haloperidol in schizophrenic patients receiving single oral dosing (6 mg/subject) have also been determined.
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For the purpose of evaluating objectively the characteristics of clinical effects of clozapine and haloperidol, a double-blind comparative trial was conducted on 91 schizophrenic in-patients. The changes of symptoms were assessed by means of several psychiatric and behavioral rating scales. The results were analyzed by means of nonparametric statistical methods. Furthermore, application of multivariate analysis was considered. After 12 weeks of treatment, though no significant difference in general improvement rate was noted between the two groups, a marked different spectrum of clinical effects was observed according to the rating scales. Clozapine is superior in anti-delusional, contact-promoting and sedative anxiolytic effect, while haloperidol is superior in anti-autistic effect. Among the side-effects, extrapyramidal symptoms appeared significatly more severe in the haloperidol group. The frequency of appearance of fever, was significantly greater in the clozapine group than the other. The four dropout cases of the clozapine group were all caused by fever. Through this clinical trial, clinical availability and validity of various statistical analytical methods were reconsidered.
Fourteen cases in which hyperpyrexia, akinesia, mutism, extrapyramidal symptoms and severe, diverse autonomic symptoms developed in the course of neuroleptic drug therapy are reported as the malignant neuroleptic syndrome, with analysis and discussion of the clinical features and pathogenic factors. Possible factors contributing to the danger of evoking this syndrome are: 1. Physical exhaustion associated with dehydration, and 2. Parenteral administration of neuroleptic agents, especially of the incisive type. Symptomatologic similarity of the syndrome to the condition known as malignant hyperthermia during anesthesia is also discussed.
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The prevalence of tardive dyskinesia was studied in two psychiatric hospitals, one in France (Hopital psychiatrique de Bassens) and the other in Japan (Inogashire Hospital). Twenty-four of 131 patients in Bassens exhibited this disorder, and 22 of 123 patients in Inogashira. No difference was observed between the prevalence of both hospitals. Higher incidence in older age and a marked coexistence of chronic brain disorders were common characteristics of the patients affected by this disorder in both hospitals. All cases in France and in Japan presented a typical oral dyskinesia, but in general the symptoms in France were less intermittent and more pronounced than those in Japan. There existed a considerable contrast of the psychotropic medications between the two hospitals, which seemed to be related not to the prevalence, but to the severity of the symptoms.