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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 19 recordsLinked to original sources
PubMed1996

Gender differences in neuroleptic nonresponsive clozapine-treated schizophrenics.

Gender differences in neuroleptic-refractory chronic schizophrenic disorder patients were examined to determine whether a superior or equivalent antipsychotic response in women vs. men existed similar to that of the general schizophrenic population. Sixty-nine DSM-III schizophrenic patients (47 males and 22 females) were treated with clozapine using a standardized medication regime. The gender differences in these neuroleptic-nonresponsive chronic schizophrenic disorder patients differed from those previously observed in the general schizophrenic population in that an equivalent antipsychotic treatment response in females versus males was not found. These treatment-refractory women appear to be a severely ill subgroup of female schizophrenics with distinct onset of illness, course and treatment response characteristics.

Adolescent↗
PubMed1996

Schizophrenia.

Explore the source record for details and available documents.

Antiparkinson Agents↗
PubMed1996

Incidence and correlates of tardive dyskinesia in first episode of schizophrenia.

BACKGROUND: There is controversy over whether tardive dyskinesia (TD) is solely a consequence of antipsychotic drug treatment or in part may reflect an intrinsic aspect of the disease process. Pathophysiologic factors could, independently or in concert with drug effects, lead to the development of dyskinetic signs. METHODS: We studied prospectively 118 patients in their first episode of psychosis who were treatment-naive or had less than 12 weeks of antipsychotic drug exposure at study entry. Patients received standardized antipsychotic drug treatment and were evaluated for up to 8 1/2 years with regular assessments of psychopathologic signs and symptoms and side effects. RESULTS: The cumulative incidence of presumptive TD was 6.3% after 1 year of follow-up, 11.5% after 2 years, 13.7% after 3 years, and 17.5% after 4 years. Persistent TD had a cumulative incidence of 4.8% after 1 year, 7.2% after 2 years, and 15.6% after 4 years. Taken individually, both antipsychotic drug dose, entered as a time-dependent covariate, and poor response to treatment of the first psychotic episode were significant predicters of time to TD. When antipsychotic drug dose and treatment response were examined together, treatment responders had significantly lower hazards for presumptive TD than nonresponders (hazard ratio, 0.29; 95% confidence interval, 0.09 to 0.97). Dose was a trend-level predicter, with each 100-mg chlorpromazine equivalent unit increase in dose associated with a 5% increase in the hazard of presumptive TD (hazard ratio, 1.05; 95% confidence interval, 0.99 to 1.11). CONCLUSION: Poor response to the treatment of a first episode of psychosis and, to a lesser extent, antipsychotic drug dose are important factors in the development of TD. This suggests that there may be a disease-related vulnerability to TD manifest with antipsychotic drug exposure. Potential pathophysiologic factors might include neurodevelopmentally induced structural neuropathologic characteristics, sensitization of nigrostriatal dopamine neurons, and the induction of glutamatergically mediated neurotoxic effects.

Adult↗
PubMed1996

Medical complications of new antipsychotic drugs.

Although antipsychotic drugs have a high therapeutic index (ratio of clinical benefit to adverse effects), they are associated with a range of adverse effects in most patients. The majority of these side effects are tolerable, readily managed, and not life threatening. The most troublesome side effects are neurological. Two new antipsychotics (clozapine and risperidone) have recently been introduced and are the first of a new generation of compounds that may further improve the therapeutic index of routine antipsychotic drug administration. Clozapine clearly has a reduced risk of drug-induced parkinsonism, akathisia, and tardive dyskinesia, while producing an increased risk of agranulocytosis, seizures, and weight gain. Risperidone at low doses produces relatively few parkinsonian side effects, but it can cause tardive dyskinesia (though relative risk remains to be established). Risperidone has not been associated with blood dyscrasias or increased risk of seizures, but weight gain can be a problem for some patients. Neuroleptic malignant syndrome has been reported with both drugs, but relative risk has not been established.

Agranulocytosis↗
PubMed1996

Serum lithium levels and psychosocial function in patients with bipolar I disorder.

OBJECTIVE: This study compared the effect of two different serum lithium levels on the psychosocial functioning of patients with bipolar I disorder. METHOD: Ninety patients with bipolar I disorder were enrolled in a prospective, double-blind, maintenance trial of lithium. The patients were randomly assigned to treatment with doses of lithium adjusted to achieve a serum lithium concentration of either 0.8 to 1.0 mmol/liter (standard) or 0.4 to 0.6 mmol/liter (low). The Longitudinal Interval Follow-Up Evaluation was used to assess psychosocial functioning in the areas of work, interpersonal relationships, and global functioning. All observed values were analyzed with a mixed-effects analysis of covariance. Independent variables included treatment group (low or standard lithium serum level), relapse status, socioeconomic status, time from random treatment assignment to assessment, termination of protocol before or after relapse, length of remission before random treatment assignment, polarity of the last mood episode before random treatment assignment, and number of mood episodes in the 3 years before random treatment assignment. RESULTS: Relapse was associated with large negative effects on psychosocial functioning. Patients in higher socioeconomic brackets had better psychosocial functioning than did those in lower brackets. Patients receiving lithium doses that achieved standard serum levels had better psychosocial functioning than those receiving doses that achieved low serum levels; this effect was partially but not wholly mediated through relapse prevention. CONCLUSIONS: For patients with bipolar I disorder, standard serum lithium levels may enhance psychosocial functioning, above and beyond the effects of relapse prevention.

Adolescent↗
PubMed1996

Treatment-resistant schizophrenic patients.

Despite the proven efficacy of antipsychotic medication in the treatment of schizophrenia, a substantial proportion of patients derive little if any benefit from traditional medications. Though alternative strategies (e.g., increasing dosage, switching antipsychotic, or adding adjunctive medication) are frequently employed, success rates are often disappointing. Clozapine has shown to be effective in some poor or partially responsive patients in three prospective, random assignment, double-blind trials. Risperidone has not yet been extensively studied in treatment-resistant patients, but may also be a useful alternative.

Antipsychotic Agents↗
PubMed1995

The enhancement of muscimol-stimulated 36C1 influx by the antispastic 5-aryl-3-(alkylsulfonyl)-4H-1,2,4-triazole (MDL 27,531) in rat brain membrane vesicles.

The antispastic triazole, 4-methyl-3-methylsulphonyl-5-phenyl-4H-1,2,4-triazole (MDL 27,531) was tested in glycine- and muscimol-stimulated 36Cl- influx into brain membrane preparations. MDL 27,531 (100 nM) had no effect on glycine- (100 nM-400 microM) stimulated 36Cl- influx in brain stem tissue; on the other hand, MDL 27,531 (10 nM-10 microM) enhanced muscimol- (1 microM) stimulated 36Cl- influx in cerebellar but not cortical membranes. In the presence of the benzodiazepine (BZD) antagonist, flumazenil (10 microM), MDL 27,531 inhibited muscimol-stimulated flux. These data suggest a novel interaction of this triazole with subtypes of the gamma-aminobutyric acid (GABA)A receptor complex and the BZD receptor.

Animals↗
PubMed1995

Risperidone: efficacy and safety.

This article reviews the evidence for the efficacy and effectiveness of risperidone in persons with schizophrenia. Nine published double-blind studies compare risperidone with another antipsychotic medication and/or placebo. All were conducted in the acute phase of illness. Risperidone's antipsychotic efficacy is shown to be consistently superior to that of placebo and at least comparable to that of haloperidol and perphenazine for patients in the acute phase of schizophrenia. Further research is necessary to determine the effectiveness of risperidone and its efficacy both as a maintenance treatment and in treatment-refractory and deficit-state patients.

Acute Disease↗
PubMed1995

Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients.

OBJECTIVE: This study assessed the prevalence of extrapyramidal signs and spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients and examined the clinical correlates. METHOD: In a prospective study of the psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive patients for the presence of extrapyramidal signs by using the Simpson-Angus Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale. RESULTS: Fifteen patients (16.9%) had extrapyramidal signs, but only one had spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was correlated with more negative symptoms and poorer treatment outcome that was reflected in a longer time to and lower level of remission. There was no correlation of spontaneous extrapyramidal signs with age of patient, age at onset of psychotic symptoms, or baseline psychopathology. There was no difference between patients with and without spontaneous extrapyramidal signs in terms of the subsequent development of persistent tardive dyskinesia, but the patients with spontaneous extrapyramidal signs were more likely to develop parkinsonian side effects after 8 weeks of antipsychotic treatment. CONCLUSIONS: Extrapyramidal signs are present in a proportion of neuroleptic-naive, first-episode schizophrenic patients, which suggests an involvement of these signs in the schizophrenic process that probably reflects basal ganglia pathology. The presence of spontaneous extrapyramidal signs seems to have prognostic significance insofar as it is linked to a poorer outcome and longer time to remission. Spontaneous dyskinesia appears to be a relatively rare finding.

Adolescent↗
PubMed1995

Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients.

OBJECTIVE: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response. METHOD: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day. Plasma clozapine levels were obtained at weeks 3 and 6, and standard clinical ratings (Brief Psychiatric Rating Scale [BPRS] and Clinical Global Impression) were done at baseline and at weeks 3 and 6. RESULTS: Data from 45 subjects were analyzed. There were no correlations between plasma clozapine levels and change in BPRS scores at treatment weeks 3 and 6. However, when the subjects were classified as responders or nonresponders, therapeutic response was associated with clozapine blood levels above 350 ng/ml. CONCLUSIONS: This study suggest that clozapine blood levels are correlated with clinical response.

Adult↗
PubMed1995

Neuroleptic treatment of elderly patients.

Data from an ongoing longitudinal study of the development of tardive dyskinesia were analyzed to examine the indications for neuroleptic treatment, continuity of treatment and dosage, and the effects of treatment on ratings of psychopathology and cognitive functioning during the first year of followup. Subjects were 266 elderly patients who had just begun neuroleptic treatment. Patients were predominantly (75%) female; their mean (+/- SD) age was 76.9 (+/- 9.2) years. A psychiatric diagnosis was recorded for 44 percent, primarily major depressive disorder; organic mental syndrome was diagnosed in 65 percent of the patients. Symptom ratings indicated 82 percent of the patients had psychosis, with or without agitation. Haloperidol was prescribed for 68 percent of the patients. Most were on neuroleptic medication continuously during the first month of followup; the average starting dose was 80 mg/day in chlorpromazine equivalent units. Symptom ratings at 1 month and 6 months showed significant improvement from baseline; ratings of dementia were unchanged.

Aged↗
PubMed1995

Antipsychotic medication in the treatment of schizophrenia.

Antipsychotic medication remains the mainstay of both acute and long-term treatment for schizophrenia. Recent research has underscored the need for optimum dosing strategies. Relatively few patients benefit from high doses (e.g. greater than 15-20 mg per day of haloperidol or 500-800 mg/day of chlorpromazine). In poor or partial responders clozapine continues to be the treatment of choice. Risperidone is an effective antipsychotic with a good safety profile. Its potential advantages in terms of efficacy need to be further studied. An expanded data base from maintenance trials supports the use of continuing maintenance medication and provides guidelines for dosage requirements.

Antipsychotic Agents↗
PubMed1995

Dosing issues and depot medication in the maintenance treatment of schizophrenia.

Antipsychotic medication has proved to be of enormous value in the long-term treatment of schizophrenia. Maintenance medication has been shown to reduce rates of relapse and rehospitalization substantially and to enable patients to benefit from psychosocial treatments and vocational rehabilitation. At the same time, improving compliance while optimizing the benefits and minimizing the risks associated with long-term drug treatment has been a major challenge. Depot medications are a valuable part of a maintenance strategy for many patients. Considerable data are now available on dose-response relationships with depot drugs, improving our ability to use them judiciously.

Antipsychotic Agents↗