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Biomedical subjects

S J Keith

Publications and source records attributed to S J Keith.

At least 19 recordsLinked to original sources
PubMed2001

Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia.

N-Acetyl-aspartate (NAA), a marker of neuronal integrity, has been found to be reduced in frontal regions in schizophrenia. However, the impact of antipsychotic drug type on NAA has not been carefully evaluated. We studied outpatients with schizophrenia/schizoaffective disorders chronically treated with haloperidol or clozapine and normal controls with single-voxel 1H-MRS of the caudate nuclei and the left frontal lobe. Concentrations of NAA, choline containing compounds (Cho) and creatine plus phosphocreatine (Cre) were determined and corrected for the proportion of cerebrospinal fluid (CSF) in each voxel. The haloperidol-treated group had significantly lower CSF-uncorrected and CSF-corrected left frontal NAA than the normal controls, with the clozapine group having intermediate concentrations. The haloperidol-treated group had significantly lower CSF-uncorrected caudate NAA than the normal controls, but the three groups did not differ after correcting for CSF fraction. Performance times in the Grooved Pegboard, a measure of motor dexterity and proxy for parkinsonism, were correlated with CSF-uncorrected and CSF-corrected left frontal NAA. Demographic and illness-related variables were not related to NAA. Exposure to haloperidol-like drugs may in part account for the frontal NAA reductions previously reported in schizophrenia. Adjustment for proportion of voxel CSF should be considered in 1H-MRS studies.

Adolescent↗
PubMed2001

Placebos and paradoxes in psychiatric research: an ethics perspective.

The use of placebos in clinical trials, particularly in research with mentally ill people, has emerged as a subject of considerable controversy. We first outline ethical aspects of the primary scientific arguments for and against placebo use in research. Three examples of paradoxical aspects of the ethical use of placebos are discussed: involvement of relatively more vulnerable populations, use of apparently "less than standard" therapy, and the omission of information in placebo comparisons. In the current scientific and regulatory context, placebo use in psychiatric research may be necessary for scientific reasons, and when certain conditions are present, it may be justified on ethical grounds. Four key recommendations to facilitate the ethical use of placebos in research trials are presented. We conclude that placebo trials should be undertaken only after careful evaluation of alternative scientific strategies and, as with all human research, with great respect and genuine consideration for the individuals who choose to participate in these protocols.

Clinical Trials as Topic↗
PubMed2001

The patient with first episode psychosis.

The authors describe their approach to the patient presenting with a first episode of psychosis. This approach differs from the treatment of established/chronic patients and is critical in insuring proper assessment and initial treatment and may possibly influence the prognosis. Using prototypical cases, the authors give an overview of the first encounter, working with the family, differential diagnosis, treatment, and prognosis.

Journal Article↗
PubMed2001

Family treatment and medication dosage reduction in schizophrenia: effects on patient social functioning, family attitudes, and burden.

The effects of 2 family intervention programs (supportive family management [SFM], including monthly support groups for 2 years; or applied family management [AFM], including 1 year of behavioral family therapy plus support groups for 2 years), and 3 different neuroleptic dosage strategies (standard, low, targeted) on social functioning of patients with schizophrenia. their relatives' attitudes, and family burden were examined. AFM was associated with lower rejecting attitudes by relatives toward patients and less friction in the family perceived by patients. Patients in both AFM and SFM improved in social functioning but did not differ, whereas family burden was unchanged. Medication strategy had few effects, nor did it interact with family intervention. The addition of time-limited behavioral family therapy to monthly support groups improved family atmosphere, but did not influence patient social functioning or family burden.

Adult↗
PubMed2001

Evaluating characteristics of patient selection and dropout rates.

Patient selection and dropout rates can affect the results of a clinical trial. Long lists of exclusions in the selection of patients for clinical trials reduce the possibility of examining treatment responses for heterogeneity and make recruitment difficult. In many cases, a pool of 100 potential subjects may yield only 2 or 3 qualified participants, a fact that raises the issue of generalizability of results. Dropouts should be carefully defined in advance and can be used as dependent variables for the comparison of different treatments. This article discusses some of the sampling characteristics (gender, age, diagnosis, inpatient/ outpatient status, prior neuroleptic use, and symptom severity) and dropout rates in 5 recent comparative clinical trials of atypical antipsychotics.

Adult↗
PubMed1999

A critical review of research on psychosocial treatment of schizophrenia.

In the following review, the evidence for the effectiveness of the psychosocial treatments of schizophrenia are evaluated. Although most studies focus on relapse and hospitalization, when available, we present information on other domains of outcome (e.g., social adjustment and employment). We begin with family treatments for schizophrenia, then intensive case management, followed by social skills training, supported employment programs, and finally, individual psychotherapy. The topics have been chosen in descending order of available critical supportive studies. Recommendations for specific psychosocial interventions (including target populations) are discussed. Overall psychosocial treatments have been shown to reduce schizophrenic relapses but have not convincingly generalized to improving other facets of the illness. Despite this, psychosocial treatments should be supported and further research to improve them is necessary.

Affect↗
PubMed1999

Sildenafil for women patients with antidepressant-induced sexual dysfunction.

In an open study, sildenafil (Viagra) was prescribed for nine women outpatients who reported sexual dysfunction induced by antidepressant medication, primarily selective serotonin reuptake inhibitors. A 50 mg dose of sildenafil was prescribed, and patients were instructed to take it approximately one hour before sexual activity. They were told to increase the dose to 100 mg on the next occasion if they experienced a partial response or a lack of response to sildenafil. The nine patients, all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances, reported significant reversal of sexual dysfunction, usually with the first dose of 50 mg of sildenafil.

Adult↗
PubMed1999

Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in 4 patients.

OBJECTIVE: To evaluate the effect of sildenafil on iatrogenic serotonergic antidepressant-induced sexual dysfunction. METHOD: Four outpatients (2 men, 2 women) who developed sexual dysfunction (erectile impotence, anorgasmia) during treatment with a serotonin reuptake inhibitor antidepressant for psychiatric disorder were selected. Each subject was initially prescribed sildenafil 50 mg to be taken approximately 1 hour before sexual activity. The dose was increased to 100 mg for a partial or failed response. RESULTS: Four cases are detailed in case report fashion. All 4 had rapid reversal of their sexual dysfunction, usually with the first dose. Reversal equates to 1 successful use of sildenafil in each of 2 patients and 3 uses in 2 patients. CONCLUSION: Sildenafil may be an effective treatment for serotonergic antidepressant-induced sexual dysfunction and deserves further evaluation in randomized placebo-controlled studies.

Adult↗
PubMed1997

Consideration of the relevance of ethological animal models for human repetitive behavioral spectrum disorders.

Treatment successes of various stereotyped behaviors in animals and humans has renewed interest in ethologic animal models for the study of psychiatric disorders. This report presents another such behavior occurring in horses to weaving. This anomalous, repetitive, and purposeless behavior draws analogies to human compulsive spectrum behaviors. A "weaver" provided an opportunity to evaluate serotonin, dopamine, and opioid neurotransmitter system contributions by probing each with a selective agent in A-B-A-C-A-D design. The horse was treated in sequential 1-month periods separated by 1-month washouts with a serotonin transport inhibitor (SRI), opiate antagonist (OA), and neuroleptic (DA). Videotape was taken weekly and analyzed by two blind raters. Frequency of head swings, latency to onset, and severity were recorded. The SRI showed > 95% symptom reduction, the DA 40%, and OA 30%. The findings suggest that neurochemical explanations of disturbance based on single drug vs. placebo trials may be oversimplified. Multiple-system probes are needed to dissect complex interactive biological systems. Animal model research can have an important role in such investigations.

Acepromazine↗
PubMed1997

Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Adolescent↗
PubMed1996

Transition from acute to maintenance treatment: prediction of stabilization.

The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization, developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed.

Antipsychotic Agents↗
PubMed1995

Maintenance treatment of schizophrenia: a review of dose reduction and family treatment strategies.

Maintenance treatment in schizophrenia requires the integration of both medication and psychosocial treatment interventions for maximum effect. We review the recent evidence for strategies drawn from both domains. For the use of anti-psychotic medication we focus on studies of dose reduction using two strategies that differ in assumptions regarding the action of medication. They are: continuous low-dose and targeted, early intervention or intermittent treatment. For psychosocial interventions we focus on studies of family treatment. Regarding dose reduction, we conclude that both strategies are feasible but the targeted strategy incurs higher relapse and rehospitalization rates. Regarding family treatment, we conclude that family treatment provides benefits beyond other psychosocial interventions or usual care, but that there is no evidence for differences in efficacy among family treatments.

Antipsychotic Agents↗