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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1994

5-Aryl-3-(alkylthio)-4H-1,2,4-triazoles as selective antagonists of strychnine-induced convulsions and potential antispastic agents.

Selected examples from three series of isomeric (alkylthio)-1,2,4-triazoles were prepared and examined for anticonvulsant activity versus strychnine-, maximal-electroshock-, pentylenetetrazole-, and 3-mercaptopropionic-acid-induced seizures in mice. A number of 5-aryl-3-(alkylthio)-4H-1,2,4-triazoles were selective antagonists of strychnine-induced convulsions. The isomeric 3-aryl-5-(alkylthio)- and 5-aryl-3-(alkylthio)-1H-1,2,4-triazoles were essentially inactive as anticonvulsants. The most potent antagonist of strychnine-induced convulsions was 5-(2-fluorophenyl)-4-methyl-3-(methylthio)-4H-1,2,4-triazole (3s), while the most selective antagonist was 5-(3-fluorophenyl)-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3aa). The anticonvulsant profiles of these 4H-1,2,4-triazoles suggested that they were acting functionally like glycine receptor agonists. Since it has recently been postulated that compounds possessing glycine-agonist-like properties might be useful in the treatment of spasticity, we examined 5-phenyl-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3c) in an in vivo model of spasticity. In this regard, 3c reduced the occurrence of hyperreflexia in rats that had received spinal transections 5-10 weeks previously. While triazole 3c appeared to possess glycine-agonist-like properties in vivo, it did not displace [3H]strychnine binding from rat brain stem/spinal cord membranes in vitro. On the other hand, 3c enhanced muscimol-stimulated 36Cl influx in a rat cerebellar membrane preparation, indicating a possible interaction of these triazoles with the GABAA receptor.

Animals↗
PubMed1994

Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia.

Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia, practical methods for identifying patients who require continuous treatment to prevent relapse have not been established. We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems, that mediates positive psychotic symptoms in the acute phase of the illness, persists in some outpatients who are vulnerable to relapse despite appearing clinically stable. To test and determine if putative measures of central nervous system dopamine activity predict outcome, 41 stable outpatients receiving neuroleptic maintenance treatment underwent provocative tests with methylphenidate in a randomized double-blind placebo controlled design in which behavioral, neuromotor, biochemical, and cardiovascular responses were measured. Patients were then withdrawn from medication and monitored for 52 weeks, or until relapse. The results indicate that psychotic symptoms and their activation by methylphenidate, and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse. These findings partially support our hypothesis and offer potentially useful measures for the identification of candidates for reduced dose neuroleptic maintenance treatment strategies in schizophrenia.

Adolescent↗
PubMed1994

Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome.

OBJECTIVE: This study addressed the unique clinical properties attributed to the atypical antipsychotic clozapine, including its efficacy in patients with treatment-refractory psychosis and against negative symptoms, its lack of acute extrapyramidal side effects, and the longer time course of its therapeutic effects. METHOD: The clinical responses of 84 schizophrenic inpatients (66 with treatment-refractory illness and 18 who were intolerant of antipsychotic treatment) were examined. After all previous antipsychotic medications had been withdrawn, the patients were treated with clozapine according to a standardized titration and dosage schedule. Patients who tolerated and responded to treatment were discharged and maintained on a regimen of clozapine for up to 52 weeks. Patients were evaluated for behavioral response and side effects after weeks 3, 6, 12, 26, 39, and 52 of treatment. RESULTS: Fifty percent of the patients with treatment-refractory illness and 76% of the treatment-intolerant patients responded to clozapine in up to 52 weeks. The optimal period for a trial of clozapine appeared to be 12-24 weeks. Clozapine exhibited therapeutic effects on negative symptoms, but these were not clearly independent of its effects on positive symptoms and extrapyramidal side effects. Several variables, including early age at onset of illness and female gender, were found to be predictors of poor response to treatment. Predictors of good response included the presence of extrapyramidal side effects during previous treatment with classic neuroleptics and a diagnosis of paranoid schizophrenia. CONCLUSIONS: These findings have important implications for the use of clozapine and our understanding of the pathophysiology of treatment-resistant schizophrenia.

Adolescent↗
PubMed1994

Risperidone.

Explore the source record for details and available documents.

Adult↗
PubMed1994

Towards more effective antipsychotic treatment.

The development of antipsychotic drugs has followed two complementary approaches, either towards highly specific actions (e.g. on the dopamine receptor) or targeting a broad range of receptors. The properties of 'atypical' agents challenge the original dopamine hypothesis and suggest roles for a variety of dopamine receptors and for other pathways, such as serotonin. Older drugs, despite their proven efficacy in relieving many schizophrenic symptoms, have several drawbacks, being ineffective in some patients, relatively ineffective against negative symptoms, and causing adverse neurological effects which may, in turn, be associated with poor compliance. Among newer agents, currently available ones, such as clozapine and risperidone, offer the possibility of more effective control of negative symptoms and an improved side-effect profile, while others are in earlier stages of development. However, much still remains to be understood about their mechanisms of action.

Agranulocytosis↗
PubMed1994

Predictors of response to clozapine.

Clinical and biological measures were examined for their relationship to clinical response to clozapine. Associations were found between therapeutic response and the following variables: male gender, paranoid schizophrenia subtype diagnosis, older age at onset of illness, shorter duration of illness, higher levels of pretreatment acute EPS, low pretreatment CSF HVA/5-HIAA, greater decrease in prolactin (PRL) and increase in growth hormone (GH) response to apomorphine stimulation pretreatment and greater inhibition by clozapine treatment of PRL and GH response to apomorphine, and plasma clozapine levels above 350 ng/mL. These results are consistent with other investigators' findings and have practical and heuristic implications for the use of clozapine and understanding its mechanism of action.

Adult↗
PubMed1994

Clozapine and weight gain.

BACKGROUND: To investigate the association of clozapine treatment and weight gain, we studied short- and long-term weight gain, correlation of weight gain with treatment response, and risk factors for weight gain in 82 patients with chronic schizophrenia who received clozapine treatment for up to 90 months. METHOD: Weight values were obtained through retrospective chart review. Clozapine was titrated over an average of 3 to 5 weeks up to a dose of 500 to 600 mg/day. Psychopathology was assessed with the Brief Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: A clinically significant weight gain occurred mostly during the first 6 to 12 months, but continued well into the third year of treatment. Weight gain and treatment response were not correlated, and early weight gain was not a predictor of response. The cumulative incidence of patients becoming substantially overweight exceeded 50%. Being underweight at baseline correlated with maximum amount gained (p = .000), and being overweight at baseline correlated with percentage above ideal weight (p = .006). CONCLUSION: Treatment with clozapine is associated with a high incidence of substantial weight gain, posing a potential long-term health risk. Studies are needed of the underlying mechanisms of weight gain, as well as the treatment for this side effect.

Adult↗
PubMed1994

Cerebral morphometry and clozapine treatment in schizophrenia.

Studies of brain morphology in schizophrenia may be informative about basic pathophysiologic processes, provide clinically useful indicators of treatment response, and lead to the identification of markers for selective treatment effects. This paper reviews findings from magnetic resonance imaging studies of patients with schizophrenia conducted at Hillside Hospital, with special attention to (1) findings that have helped distinguish patients who respond well to typical neuroleptics from those who have gone on to trials of clozapine, (2) the capacity of morphological measures to predict clozapine treatment response, and (3) the possibility that selective hypertrophy of striatal structure may be caused by chronic treatment with typical neuroleptics, but not by clozapine.

Atrophy↗
PubMed1994

Clozapine, negative symptoms, and extrapyramidal side effects.

The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism. We report data from a cohort of 56 clozapine-treated patients demonstrating significant correlations between measures of akinesia and anergia. Despite an average drug washout of over 2 weeks, the persistence of drug-induced parkinsonism can confound the assessment of therapeutic drug effects on negative symptoms.

Adolescent↗
PubMed1994

Clozapine dose in the United States and Europe: implications for therapeutic and adverse effects.

The report (1) provides an overview of clozapine doses used in trials conducted in Europe and the United States, (2) compares data on efficacy, and (3) compares side effects of clozapine from recent European and U.S. investigations. The reviewed European trials used a mean dose of 283.7 mg/day, while the mean dose in the U.S. studies was 444 mg/day. Even though the mean doses used in the United States are considerably higher than those used in Europe, the response rates for the two continents are strikingly similar. The main differences in a comparison of two samples evaluated in New York and Innsbruck were found in the prevalence of seizures (Innsbruck, 0%; United States, 7.1%) and confusion (Innsbruck, 0%; United States, 14%). Excitement was less prevalent in the U.S. study. The data presented appear to suggest that a lower dose of clozapine may be as effective as a higher dose in the management of treatment-resistant schizophrenic patients and may cause fewer side effects.

Akathisia, Drug-Induced↗
PubMed1994

The use of clozapine in neurologic disorders.

The advent of clozapine has marked a major advance in the treatment of schizophrenia because of its low incidence of extrapyramidal side effects and superior efficacy. Because of a relatively high incidence of agranulocytosis, approved indications for use are limited to treatment-refractory or neuroleptic-intolerant patients with schizophrenia. However, an emerging body of literature suggests that clozapine may be preferable to typical neuroleptics for treating psychosis in certain neurologic disorders. In addition, clozapine may have a place in the treatment of movement disorders that are caused by or are a result of the pharmacologic treatment of some neurologic illnesses. In general, clozapine doses used in these settings are lower than that for treating psychosis in schizophrenia. This article reviews the experience with clozapine in selected neurologic disorders.

Clinical Trials as Topic↗
PubMed1993

Psychopharmacologic treatment of schizophrenia.

Antipsychotic (neuroleptic) medications continue to be a critical component in the treatment of schizophrenia. Despite numerous advances in brain imaging, genetics, and neurochemistry, the pharmacologic agents routinely used to treat schizophrenia have not changed markedly over the last 30 years. The introduction of clozapine, however, represents an important step in drug development and has stimulated renewed activity in this area. In addition, its novel effects have had a heuristic value in efforts to better understand neuropharmacologic mechanisms. While we await further advances in treatment development, we are benefiting from clinical research focusing on improving our ability to use available pharmacotherapy in the most effective and least toxic manner. Recent studies reemphasize the potential value of using the minimum effective dosage for acute treatment (e.g., 10-15 mg/day of oral haloperidol) and provide needed data on the benefits and risks of long-term dosage reduction strategies (i.e., continuous low-dose or targeted/intermittent treatment).

Antipsychotic Agents↗
PubMed1993

Polydipsia and tardive dyskinesia in chronic psychiatric patients--related disorders?

Dopamine supersensitivity, presumably playing a role in tardive dyskinesia, has been implicated in the unexplained polydipsia occurring in chronic psychiatric patients. To investigate this hypothesis, the authors compared laboratory measurements indicating the fluid status of 65 patients before and after the development of tardive dyskinesia. No evidence was found that patients who develop tardive dyskinesia concurrently develop abnormalities in fluid regulation.

Adolescent↗