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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 145 records · Page 8Linked to original sources
PubMed1988

Clozapine-induced agranulocytosis: non-cross-reactivity with other psychotropic drugs.

Clozapine, an atypical neuroleptic with unique clinical and preclinical properties, represents a potentially valuable addition to the psychopharmacopeia. Its development and use have been limited by its higher frequency, compared with other pharmacologic treatments, of the potentially fatal side effect of agranulocytosis. This article describes the natural history of five cases of agranulocytosis that occurred in the course of clozapine treatment. The cases were generally uniform as to onset, recovery, and hematologic features. No patient had hematologic reactions to treatment with psychotropic agents before or after clozapine treatment. These findings, along with other work in progress, suggest that clozapine's granulocytoxic effects are produced by a highly specific immune-mediated mechanism.

Adult↗
PubMed1987

Prediction of relapse in schizophrenia.

Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia, practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking. This study evaluated the use of a methylphenidate challenge test to predict the outcome in 34 stable outpatients with schizophrenia receiving neuroleptic treatment. Patients received two infusions, one of methylphenidate and one of placebo, in randomized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal. Behavioral, cardiovascular, and neurologic responses were evaluated before and after infusion under double-blind conditions. Patients were then followed up without medication for 52 weeks or until symptom recurrence. The results indicate that specific measures, including behavioral response to methylphenidate, presence of tardive dyskinesia, and, under specific pharmacologic conditions, tardive dyskinesia, blink-rate, and pulse-rate responses to methylphenidate, are associated with time and propensity to relapse following neuroleptic withdrawal. These measures may be potentially useful in the identification of candidates for neuroleptic withdrawal and/or dosage-reduction treatment strategies.

Adolescent↗
PubMed1987

Provocative tests with psychostimulant drugs in schizophrenia.

The psychotogenic effects of psychostimulant drugs have provided a major line of evidence in support of the DA hypothesis of schizophrenia. To evaluate the effects of psychostimulant (PS) drug in schizophrenia and the clinical variables which may influence their expression, we reviewed 36 studies of PS drugs in patients with schizophrenia. Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normals. Specific clinical variables appear to modify this response, including diagnosis, degree and type of psychopathology, stage of illness and pharmacologic status at the time of testing. Non-amphetamine-like PS drugs, e.g., methylphenidate, appear to have greater psychotogenic potency than amphetamine-like PS drugs. These results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion. This biologic phenomenon may be clinically exploitable and should be investigated further.

Antipsychotic Agents↗
PubMed1987

Treatment of schizophrenia.

Antipsychotic medication remains a mainstay of treatment in both acute and chronic schizophrenia. Emphasis in recent years has focused on maximizing benefits and minimizing risks of medication by attempting to establish minimum effective dosage requirements for all phases of treatment and to provide alternative strategies for individuals who fail to benefit from antipsychotic drug treatment. At present all approaches to the treatment-refractory patient remain experimental, and further research in this area is of critical importance. Definite advances have been made in exploring the impact of psychological and psychosocial treatments administered in conjunction with various antipsychotic drug strategies. More sophisticated and comprehensive assessment measures have been applied in long-term treatment trials, enabling us to be more specific about treatment goals and treatment evaluation. Although no major "breakthrough" has occurred in the treatment of schizophrenia, incremental advances which can reduce rates of relapse and rehospitalization, improve the quality of adaptation, and reduce the risk of significant adverse effects are of enormous importance to affected individuals, their families, and society at large.

Antipsychotic Agents↗
PubMed1986

Outcome study of first-episode psychosis. I: Relapse rates after 1 year.

One-year relapse rates were assessed in a group of 64 patients diagnosed by Research Diagnostic Criteria who were hospitalized for their first psychotic episode. Life-table analysis showed that of the 51 remitted patients, 71.4% of the schizophrenic patients (N = 20), 71.4% of patients with affective disorders (N = 10), and 77.8% of patients diagnosed as having either unspecified functional psychosis or other psychiatric disorder (N = 7) remained in remission at 1-year follow-up. Factors associated with relapse or poor outcome (patients who remained in episode) included no maintenance medication, longer duration of illness, and premorbid asociality.

Adult↗
PubMed1986

Dosage strategies with long-acting injectable neuroleptics, including haloperidol decanoate.

Concern about the dose of neuroleptic drugs has become widespread in recent years. This concern largely has been prompted by recognition of the apparent relationship between neuroleptic dose and potential adverse effects, such as tardive dyskinesia and extrapyramidal symptoms. Therefore, it is critical to establish dosing strategies for long-term therapy that emphasize a minimal effective dose. Such a dosing strategy for long-acting injectable neuroleptics, including haloperidol decanoate, is highlighted. A low initial dose of the long-acting drug is recommended, with gradual dosage adjustment over an extended period of time. General guidelines for using oral supplementation are also provided.

Antipsychotic Agents↗
PubMed1986

Depot neuroleptics: a comparative review of standard, intermediate, and low-dose regimens.

New research in maintenance drug therapy has been influenced by a need to clarify risk-benefit ratios and determine minimum effective dosages. This research employing controlled study designs and new methods of data analysis has increased our ability to apply findings to specific patients, families, and treatment settings. Results from studies using depot neuroleptics indicate that this methodology may clarify the correlation between dose and blood levels and thus lead to the establishment of generalizable dosage guidelines. Lack of knowledge of maintenance requirements with long-acting injectable drugs may have led to the use of higher doses than necessary and an increased incidence of side effects. Recent studies suggest that with careful clinical observation, substantial reduction of maintenance doses can, for many patients, lead to improvement in some areas of subjective and objective well-being and to a diminution of adverse effects.

Antipsychotic Agents↗
PubMed1986

Neuromuscular effects of monoamine oxidase inhibitors.

The MAOI class of drugs is known to produce neuromuscular effects at therapeutic and toxic doses when given alone or in combination with other drugs. These effects range from muscle tension and twitches in their mild form to forceful myoclonic jerks. These effects may also be part of a more pervasive toxic syndrome that includes autonomic and mental symptoms as well. There is meager direct and substantial indirect evidence that serotonergic mechanisms play a role in mediating the neuromuscular effects of MAOIs. We have hypothesized that MAOIs produce a condition of heightened neuromuscular excitability due to a combination of increased serotonergic tone and central disinhibition of alpha-motor neuron-mediated spinal activity. Further study is needed utilizing objective pharmacologic and neurophysiologic measures.

5-Hydroxytryptophan↗
PubMed1985

Schizophrenics with tardive dyskinesia. Neuropsychological deficit and family psychopathology.

We investigated the role neurologic soft signs, premorbid asociality, psychometric tests, and family history of psychiatric illness may play in the identification of patients at risk for tardive dyskinesia (TD) development. Thirty-two TD and 32 non-TD schizophrenics served as subjects. The results indicated that patients with TD have more soft signs, are more frequently rated as poor premorbid asocials, perform more poorly on psychometric testing, and have a familial loading for affective disorders in first-degree relatives higher than control patients. A discriminant function analysis correctly classified 84.4% of the patients into their respective groups. Subtle yet quantifiable differences exist between TD and non-TD patients and these deficits may render the individual more vulnerable to TD development.

Adult↗
PubMed1985

The Cognitive Deficit subscale of the SCL-90-R and prediction of outcome in first episode schizophrenics.

This study examined the relationship between the Cognitive Deficit scale and psychiatric outcome in a sample of 31 first episode schizophrenics. These patients initially were evaluated during their inpatient hospitalization and thereafter assessed for psychiatric symptomatology at 3-, 6-, and 12-month intervals. At the end of 12 months, 51.6% of the sample were in remission, and 48.4% either remained in their psychotic episode during the follow-up period or relapsed. However, the two Cognitive Deficit scores obtained at baseline showed no relationship with subsequent outcome of psychiatric illness. It is suggested that this scale may not be sensitive enough to be used as a diagnostic tool with this group of patients.

Adult↗
PubMed1985

Tardive dyskinesia: prevalence, incidence, and risk factors.

Tardive dyskinesia remains a major concern in psychiatry. Epidemiologic data suggest that the prevalence of the disorder has increased over the past two decades. The average prevalence of TD across various populations is 15%-20%. Abnormal involuntary movements appear to be at least three times more prevalent in neuroleptic-treated patients than in patients not exposed to such drugs. The incidence of TD in a young adult (mean age 27) population is 14% after 4 years of cumulative neuroleptic exposure. The majority of these cases are mild and the condition does not appear to progress in most individuals despite continued neuroleptic exposure. Age remains the single most important risk factor for the development of TD. Recent investigations suggest that patients with affective illness may also be more vulnerable.

Adult↗
PubMed1985

Cognitive impairment in tardive dyskinesia.

Psychiatric patients in a prospective study on tardive dyskinesia (TD) development were psychometrically evaluated before TD onset to see whether cognitive impairment predisposes an individual to greater risk for TD. It was found that patients with TD showed more preexisting cognitive impairment than did the non-TD controls.

Adult↗
PubMed1985

Tricyclic antidepressant and metabolite levels in chronic renal failure.

Serial blood samples were drawn from 12 patients undergoing hemodialysis who were receiving tricyclic antidepressants (TCAs). Samples were drawn before, during, and after a dialysis session (two to 17 sessions per subject). Samples were analyzed by HPLC before and after hydrolysis with beta-glucuronidase/sulfatase to determine the conjugated and nonconjugated metabolites. Analysis of these data in comparison with those of controls with depression and normal renal function showed that: (1) at steady state, tertiary and secondary amine TCA levels did not differ; (2) levels of the hydroxylated metabolites had greater variability and were somewhat higher at steady state; (3) levels of the conjugated hydroxylated compounds were markedly elevated, reaching 500% to 1500% normal; (4) the time to reach a steady-state level appeared to be slightly increased; and (5) elimination t1/2 s of unconjugated and conjugated drug forms were longer in our patients with normal renal function than those reported in the literature. Levels of the tertiary, secondary, and hydroxylated metabolites were not changed by dialysis, whereas there were substantial decrements in glucuronidated metabolite levels. These findings demonstrate increased concentrations of conjugated drug forms and suggest an abnormal distribution or delayed elimination of unconjugated and conjugated metabolites. These observations may shed some light on the apparent hypersensitivity of these patients to TCA side effects, particularly because glucuronides may exert peripheral pharmacologic effects.

Adult↗