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Biomedical subjects

W M Glazer

Publications and source records attributed to W M Glazer.

At least 19 recordsLinked to original sources

Race and tardive dyskinesia among outpatients at a CMHC.

OBJECTIVE: In a previous study of outpatients with chronic mental illness who were treated with neuroleptic medication, the authors found a higher incidence of tardive dyskinesia among blacks than among whites. In this study the authors examined psychosocial, clinical, treatment, and medical correlates of race that might explain this finding. METHODS: Extensive baseline data were obtained for 398 outpatients at risk for tardive dyskinesia. Pearson and Mantel-Haenszel chi square analyses were used to determine significant associations between a large number of variables and race. RESULTS AND DISCUSSION: Compared with whites, nonwhites were more likely to be younger, less skilled, and unmarried; to report contacts with relatives outside the home; to have a diagnosis of schizophrenia; and to receive higher doses of neuroleptic drugs primarily through depot medications. Nonwhites were less likely to receive nonneuroleptic psychotropics, to wear dentures, and to report social contact with fathers. None of these racial differences explained more than a trivial portion of the association between race and the incidence of tardive dyskinesia. CONCLUSIONS: These results suggest the need for studies of differences in diagnostic and prescribing practices for black and white patients and of differences in the action and side effects of neuroleptics.

Adult

Identifying risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medications. Results of the Yale Tardive Dyskinesia Study.

OBJECTIVES: To describe the incidence of tardive dyskinesia (TD) in the Yale TD Study and to identify demographic, treatment, and clinical risk factors for TD occurrence. DESIGN: An ongoing prospective cohort study in which subjects have been examined every 6 months since 1985. SETTING: The outpatient division of the Connecticut Mental Health Center in New Haven. SUBJECTS: Three hundred ninety-eight adult outpatients who had been maintained with neuroleptics for 3 months to 33 years at intake and who were free of persistent TD at intake with no history of persistent TD movements. OUTCOME MEASURE: New cases of persistent TD were defined as the presence of mild or more severe dyskinetic movements at two successive follow-up visits, using the Abnormal Involuntary Movement Scale. RESULTS: As of July 1, 1990, there were 62 new persistent cases of TD, yielding an average incidence rate of 0.053 per year and a 5-year risk of 20%. The TD rate was positively affected by age, being nonwhite, and neuroleptic dose, and it was inversely affected by years of previous exposure. Little or no effects were found for age at first neuroleptic exposure, type of neuroleptic, use of other psychiatric medications, and psychiatric diagnosis. CONCLUSIONS: For outpatients maintained for many years with neuroleptics, dose should be minimized to reduce the risk of TD. This strategy does not appear to be negated by prescribing frequent changes in dosage. Although the TD rate is greatest during the first 5 years of neuroleptic treatment, new persistent cases continue to occur many years after first exposure.

Adult

Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications.

BACKGROUND: Tardive dyskinesia (TD) has been a source of great concern to the psychiatric community because of the iatrogenic nature of the illness. Little is known about the risk of developing TD if neuroleptic medications are continued. METHOD: This paper presents long-term risk estimates for TD in a prospective cohort study of 362 chronic psychiatric outpatients who were free of TD at baseline and who were maintained on neuroleptic medications. RESULTS: On the basis of 5 years of follow-up, we estimate the risk of persistent TD to be 32% after 5 years of neuroleptic exposure (95% confidence interval [CI] = 23%-43%), 57% after 15 years of exposure (95% CI = 47%-66%), and 68% after 25 years of exposure (95% CI = 58%-77%). For patients with 10 years of previous neuroleptic exposure, the risk is 15% after 5 more years of exposure (95% CI = 7.2%-27%) and 38% after 15 more years of exposure (95% CI = 24%-53%). Our results fall within the wide range of results found in other studies of TD incidence. Differences in incidence across studies may be explained in terms of patient characteristics and other methodological factors. CONCLUSION: One implication of this finding is that patients in the first 5 years of exposure could be targeted for prevention programs if resources are limited. A potential methodological problem encountered when studying chronically exposed patients is that they may have acquired TD (persistent) prior to the study and remitted before entry.

Adult

The determination of the steady-state pharmacokinetic profile of fluphenazine decanoate by gas chromatography/mass spectrometry detection.

This study uses the highly sensitive method of gas chromatography/mass spectrometry to compare the basic steady-state pharmacokinetic parameters of two fluphenazine decanoate formulations. Sixteen stable outpatients participated in a two-way crossover design study of the bioavailability of a new formulation of FPZ Dec, i.e., 10 mg/ml, to the standard 25 mg/ml formulation. When compared to a 1 ml injection of the standard formulation (25 mg/ml) over a two-week, steady-state period, we found bioequivalence as evidenced by similar mean areas under the curve (hrs x ng/ml). We did find that the injection volume of the same dose (2.5 ml of a 10 mg/ml formulation) results in a statistically significantly higher maximum serum level of parent fluphenazine. A tendency toward faster time to peak level was observed with the 10 mg/ml formulation but the difference was not statistically significant. Both of these differences are considered too small to be clinically significant. In a subgroup of 10 patients, pre-injection serum fluphenazine levels correlated significantly (Pearson r = 0.78, p < 0.05) with serum prolactin levels.

Adult

Depot neuroleptic therapy: an underutilized treatment option.

BACKGROUND: Depot neuroleptics are effective as long-term maintenance therapy in chronic schizophrenia and are widely used in Europe. In the United States, however, physicians have been reluctant to use them. They assume that depot neuroleptics present an increased risk of major side effects, that patients do not accept or tolerate them as well as oral agents, and that prescribing depot neuroleptics increases the possibility of medicolegal problems. METHOD: We analyzed the published data on neuroleptic malignant syndrome, tardive dyskinesia, extrapyramidal symptoms, perceptions of depot therapy, and medicolegal concerns. Whenever possible, we used the Mantel-Haenszel test to compare the outcome of oral versus depot neuroleptic medication treatment. RESULTS: Depot neuroleptics are not associated with an increase in any of the negative outcomes assessed. CONCLUSION: Depot neuroleptics represent a valuable treatment option for many patients and merit wider use.

Administration, Oral

N400 and semantic categorization in schizophrenia.

The N400 component of event-related potentials (ERPs) was investigated in medicated schizophrenic patients and normal controls in a semantic categorization task. The subjects' task was to indicate whether pairs of words were semantically related or unrelated. The ERPs to the unrelated second words of the pairs contained a negative component, N400, which was reduced and delayed in the patients. However, inspection of individual subjects' data indicated that N400 was abnormal only in a subgroup of schizophrenics. Abnormalities in the amplitude of N400 suggest impairments in semantic expectancies, whereas abnormalities in the latency of N400 suggest a delay in information processing.

Adult

Intermittent vs maintenance medication in schizophrenia. Two-year results.

This is a 2-year, double-blind, placebo-controlled study of 101 patients, evaluating the relative efficacy of intermittent medication (given only when the patient shows early signs of relapse) compared with moderate doses of maintenance medication for stable schizophrenic outpatients. Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks. Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46% of intermittently treated patients. Relapse rates were 16% for patients given maintenance treatment and 30% for intermittently treated patients, a nonsignificant difference. Intermittently treated patients were receiving significantly less medication, but there were no differences found in drug side effects. There appears to be no advantage in using the intermittent approach, but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients.

Adult

The prediction of chronic persistent versus intermittent tardive dyskinesia. A retrospective follow-up study.

Relatively little is known about the course of TD in patients continuing to receive neuroleptic medication. In a retrospective follow-up study of 192 patients seen two or more times (average 7.7 visits) over 3-55 months in the Yale Tardive Dyskinesia Clinic, 112 (58%) demonstrated a 'chronic persistent' pattern, the remainder an 'intermittent' pattern. The most important predictors of chronic persistent TD, using multiple logistic-regression analyses, included increased age and the presence of non-orofacial TD at baseline.

Antipsychotic Agents

Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication.

Forty-nine chronic psychiatric out-patients (ten were schizophrenic) with tardive dyskinesia (TD) were examined monthly for a mean of 40 weeks (range 1-59 months) after discontinuation of neuroleptic medication. Complete and persistent reversibility of TD was rare (2%), but many patients showed noticeable improvement in movements within the first year of discontinuation, which was sometimes interrupted by psychological relapse. Using three separate outcome measures and appropriate model-fitting techniques for each, we identified several predictors of improvement in TD, including an affective or schizoaffective psychiatric diagnosis, chronic (over 20 years) psychiatric illness, being employed, younger age, and increased neuroleptic dose before discontinuation. Consistent findings emerging from these analyses suggest that the type and history of psychiatric illness affect the course of TD.

Adult

The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia.

As some of the pharmacological activities of neuroleptic medication may involve pathophysiological mechanisms underlying schizophrenia and tardive dyskinesia (TD), it is useful to study patients undergoing medication discontinuation. In this study, 19 stable, neuroleptic-maintained patients with persistent TD underwent taper and discontinuation of their neuroleptic medication over a 3-week period, and multiple behavioral and biochemical (plasma HVA, MHPG, and prolactin) measures were obtained. The major finding was that early relapsing patients had lower baseline and a significantly greater increase in plasma HVA levels after discontinuation than nonrelapsing patients. In addition, patients exhibiting withdrawal-exacerbated TD had significantly lower plasma MHPG levels than patients not exhibiting this phenomenon. The clinical and pharmacological implications of these findings are discussed.

Antipsychotic Agents

Platelet monoamine oxidase activity and tardive dyskinesia.

A few studies of chronic psychiatric inpatients have reported an inverse association between platelet monoamine oxidase (MAO) activity level and tardive dyskinesia (TD). In contrast to these earlier findings, we found no significant or consistent association between platelet MAO activity level and TD occurrence when we controlled for other TD predictors in a case-control study of 80 outpatients maintained on neuroleptic medications. We did find, however, that black subjects had significantly lower levels of MAO activity than did whites in an analysis controlling for age, sex, and neuroleptic dose.

Adult

Heterogeneity of tardive dyskinesia. A multivariate analysis.

To determine whether tardive dyskinesia (TD) is a single abnormal movement syndrome or multiple syndromes involving different anatomical areas, we examined 228 out-patients diagnosed with TD at the Connecticut Mental Health Center in New Haven. Application of factor analysis to the seven anatomical severity scores of the Abnormal Involuntary Movement Scale yielded three statistically independent factors involving abnormal movements primarily of the jaw-tongue, face-lips, and extremities-trunk. Using logistic regression to predict the severity of these factors, we found that the severity of the orofacial scores was positively associated with age, schizoaffective or affective disorder, and living alone, while severity of non-orofacial movement was positively associated with current neuroleptic dose, non-use of psychiatric medication, and living alone. Our findings suggest that orofacial and non-orofacial dyskinetic movements may involve distinct clinical syndromes of TD, each having a different set of prognostic and, possibly, aetiological determinants.

Adult