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W T Carpenter

Publications and source records attributed to W T Carpenter.

At least 19 recordsLinked to original sources
PubMed1999

Sense and nonsense: an essay on schizophrenia research ethics.

In this essay, the authors select topics from the current debate on the ethics of schizophrenia research. Accepting competent and voluntary informed consent as essential for most projects, the authors discuss the relation of diagnosis to decisional capacity, the respective roles of psychosis and cognitive impairments in decisional capacity, and whether impairments in capacity can be remediated. The roles of investigator, external agent, patient subject, and family or surrogate in the informed consent process are reviewed. A lack of understanding of the treatment of persons with schizophrenia has distorted and inflamed public discussion of issues such as 'withholding treatment'. A standard, based in common sense, is proposed: for viewing protocols; for allowing autonomy and altruism despite diagnostic class; and, for a meaningful discussion of what is meant by and what should be done about 'risk without direct benefit' protocols.

Antipsychotic Agents↗
PubMed1999

Diazepam treatment of early signs of exacerbation in schizophrenia.

OBJECTIVE: Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment. METHOD: A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy. RESULTS: Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine. CONCLUSIONS: Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy.

Acute Disease↗
PubMed1999

Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.

OBJECTIVE: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. RESULTS: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.

Adult↗
PubMed1999

Stability of the diagnosis of deficit syndrome in schizophrenia.

OBJECTIVE: Primary, enduring negative symptoms have been distinguished from negative symptoms more generally and are used to define the deficit syndrome of schizophrenia. Although the validity of the deficit syndrome has been demonstrated by using brain imaging, neuropsychological, illness outcome, and developmental history data, the stability of this diagnostic category has not been tested prospectively by using direct patient assessments. METHOD: Forty-three outpatients with schizophrenia and schizoaffective disorder were categorized into deficit and nondeficit groups an average of 3.8 years after having been previously categorized. RESULTS: There was 83% agreement between initial and blind follow-up designations of deficit status and 88% agreement on the nondeficit categorization. CONCLUSIONS: These results provide evidence for the long-term stability of the deficit syndrome in patients with schizophrenia and the reliability of the deficit/nondeficit categorization when diagnosed by those with appropriate training. Furthermore, they validate the method of categorizing deficit patients by using cross-sectional and retrospective data.

Adult↗
PubMed1998

Medical-claims databases in the design of a health-outcomes comparison of quetiapine ('Seroquel') and usual-care antipsychotic medication.

Treating schizophrenia is expensive. Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings, especially for patients with 'revolving-door' or multiple-episode schizophrenia. Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with standard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia. Quetiapine ('Seroquel', ICI 204,636, Zeneca Pharmaceuticals) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms. We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment settings. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and, therefore, treatment costs. Using two secondary medical-claims databases, we defined the minimal threshold for revolving-door status as 1.0 admission per year; this definition allows our trial to focus on the subpopulation of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy. We describe here the approach used in our trial.

Adolescent↗
PubMed1998

Hypothesis testing: is clozapine's superior efficacy dependent on moderate D2 receptor occupancy?

BACKGROUND: How clozapine exerts superior antipsychotic efficacy in treatment-resistant schizophrenia is not known. Moderate (rather than "full") occupancy of D2 postsynaptic receptors may be crucial, perhaps by achieving a more effective D1/D2 or serotonin-2a/D2 ratio. The objective of this study was to test the moderate occupancy hypothesis of clozapine's superior efficacy. METHODS: Data from the New York effectiveness of clozapine study were used to compare 6-week clozapine treatment results in patients discontinuing oral neuroleptic medication with similar patients discontinuing long-acting depot neuroleptic. The latter group is assured "full" D2 occupancy during the 6-week clozapine treatment. RESULTS: If moderate occupancy is crucial for superior efficacy, the oral discontinuation group should manifest more improvement. Both groups showed the 6-week improvement expected with clozapine therapeutics [31% and 29% reduction in Brief Psychiatric Rating Scale (BPRS) scores in the depot and oral groups, respectively]. An analysis of covariance (for baseline BPRS) revealed no difference in change scores (df = 1,100; F = 0.17; p = ns). CONCLUSIONS: The reduced D2 occupancy hypothesis is rejected.

Antipsychotic Agents↗
PubMed1998

Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome.

OBJECTIVE: In a preliminary report, the authors observed that clozapine was superior to haloperidol in the treatment of positive and negative symptoms in stable outpatients with schizophrenia. In this final report, they examine the effects of clozapine on positive and negative symptoms in patients with and without the deficit syndrome to determine which patients receive the positive symptom advantage of clozapine and the extent of clozapine's therapeutic effects on negative symptoms. In addition, they examine the long-term effects of clozapine on positive, negative, and affective symptoms, social and occupational functioning, and quality of life. METHOD: Seventy-five outpatients with schizophrenia, who met retrospective and prospective criteria for residual positive or negative symptoms, were entered into a 10-week double-blind, parallel-groups comparison of clozapine and haloperidol. Patients who completed the double-blind study were then entered into a 1-year open-label clozapine study. RESULTS: For patients who completed the 10-week double-blind study, clozapine was superior to haloperidol in treating positive symptoms. This effect was not observed in the intent-to-treat analyses. There was no evidence of any superior efficacy or long-term effect of clozapine on primary or secondary negative symptoms. Long-term clozapine treatment was associated with significant improvements in social and occupational functioning but not in overall quality of life. CONCLUSIONS: For schizophrenic patients who are able to tolerate clozapine therapy, clozapine has superior efficacy for positive symptoms but not negative symptoms and is associated with long-term improvements in social and occupational functioning for patients with and without the deficit syndrome.

Adult↗
PubMed1997

Borna disease virus antibodies and the deficit syndrome of schizophrenia.

We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p < 0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia.

Adult↗
PubMed1997

The rationale and ethics of medication-free research in schizophrenia.

Schizophrenia research is receiving intense scrutiny from an ethical perspective. Medication-free protocols present a most vexing dilemma in that they greatly enhance the opportunity for advancing knowledge but also raise the prospect of withholding known effective treatment. In this article, we discuss the purpose of medication-free protocols in new drug development and nontreatment research. Potential benefits and risks associated with drug discontinuation are evaluated, and methods for minimizing risk and increasing benefits are proposed as guidelines for the protection of individual subjects. The complex problem of informed consent also is addressed. Medication-free research in schizophrenia is difficult, but it can be conducted relatively, safely with freely consenting, competent subjects. Assurance that studies meet this standard is required. We believe that such investigations can meet high standards of ethics and subject protection, and that a radical revision of procedures for research review and implementation is not indicated.

Acute Disease↗
PubMed1997

The risk of medication-free research.

An aspect of the ethics of the medication-free research debate is the question of long-lasting damage from short-term psychosis. Data from medication-free research refute the hypothesis that short-term increase in psychosis during research causes long-term deterioration. More compelling are the preneuroleptic biased cohort studies, which suggest that years of untreated psychosis increase the incidence of poor outcome cases. Comprehensive treatment involves many therapeutic elements. In regard to pharmacotherapy, it is generally the case that the more aggressive drug treatment is associated with less psychosis, but more negative symptoms, poorer medication compliance, more depression, and more adverse drug effects. These complexities must be considered in evaluating ethical and safety issues. Standards should be high, and the evidence suggests that treatment in the context of research can (and usually does) meet these standards.

Antipsychotic Agents↗
PubMed1997

The neuroanatomies of schizophrenia.

Schizophrenia is a brain disease whose pathophysiology has escaped detection despite intensive investigation. The failure to delineate the neuroanatomy of schizophrenia is related in part to both the subtle nature of the neuropathological abnormalities and to the failure to address adequately the pathophysiological heterogeneity of schizophrenia. The symptoms of schizophrenia aggregate into relatively independent symptom complexes, which suggests that there may be a distinct neural substrate for each complex. If this is true, then the neuroanatomy of schizophrenia is better addressed as the separate neuroanatomies of symptom complexes. However, the use of symptom complexes to guide future neuroanatomical investigations raises crucial methodological issues, including the differentiation of primary versus secondary symptoms, trait versus state characteristics, and continuous versus categorical variables. Decisive hypothesis testing requires that these issues be addressed in study design.

Brain↗
PubMed1997

Attentional impairments in deficit and nondeficit forms of schizophrenia.

OBJECTIVE: Previous studies of attention/information processing impairments in schizophrenia suggest that patients with the deficit syndrome should be characterized by impaired performance on measures of visual information processing. Therefore, the authors examined whether two measures of visual information processing, a degraded stimulus version of the continuous performance test and a forced choice span of apprehension task, were uniquely related to the deficit syndrome. METHOD: Performance on the continuous performance test and span of apprehension task was examined in 20 deficit and 56 nondeficit patients with schizophrenia and in 27 subjects in a normal comparison group. RESULTS: Deficit patients performed significantly less well than both nondeficit patients and the normal comparison group on the continuous performance test and span of apprehension task. There were no significant differences between the nondeficit patients and the normal group on the continuous performance test, but nondeficit patients performed significantly less well on the span of apprehension task than the normal group. Differences between the deficit and nondeficit patients in performance on the continuous performance test and span of apprehension task were not related to total scores on the Brief Psychiatric Rating Scale factor 1 or on the Thought, Language, and Communication scale or to neuroleptic level. CONCLUSIONS: The results suggest that deficit patients are uniquely characterized by impaired performance on the continuous performance test. The deficit patients' differential performance on the continuous performance test may be related to either an inability to activate and allocate attention or an impairment in the perceptual organization of visual information.

Adult↗
PubMed1997

Visual information-processing impairments in deficit and nondeficit schizophrenia.

OBJECTIVE: Previous studies of covert visuospatial attention in schizophrenia suggest a subtle form of right hemispatial neglect in acutely ill patients but not in chronic, stable patients. Because of previous work documenting various visual information-processing abnormalities in deficit schizophrenia, the authors investigated whether the deficit/nondeficit categorization would help clarify the presence of visual attentional asymmetries in schizophrenia. METHOD: Performance on a covert visuospatial attention task was examined in clinically stable outpatients with schizophrenia (17 in a deficit subgroup and 28 in a nondeficit subgroup) and 25 normal subjects. Peripheral cue and central cue versions of the covert visuospatial attention task, at 100-, 200-, and 800-msec intervals between cue and target, were administered a week apart. RESULTS: The nondeficit patients exhibited a significant and abnormal asymmetry, with slower reaction time to targets presented in the right visual field than in the left visual field. This right visual field disadvantage was found with both versions of the task, but only at the 100-msec cue-target interval. The deficit patients were slowest in overall reaction time but, similar to the normal subjects, showed no asymmetry. CONCLUSIONS: The results are consistent with slower visual information processing in the left compared to the right cerebral hemisphere in nondeficit schizophrenia. This finding cannot be accounted for by differences between the deficit and nondeficit subgroups in demographic characteristics, chronicity, or medication effects, nor is it secondary to generalized cognitive impairment.

Adolescent↗
PubMed1997

Time to clozapine response in a standardized trial.

OBJECTIVE: The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia. METHOD: Antipsychotic response to a clozapine trial was examined in 50 treatment-refractory schizophrenic inpatients. Subjects were treated with clozapine for at least 12 months, regardless of response status, according to a standardized, increasing dose protocol. Behavioral changes were measured through monthly assessments with the Brief Psychiatric Rating Scale. RESULTS: Thirty-four subjects (68%) met clinical response criteria by the end of the trial. Response was achieved at a mean dose of 468 mg/day (SD = 168). The dose of 30 (88%) of the responding patients was 600 mg/day or less. The mean time to response was 82 days (SD = 100, range = 10-401). It took an average of 60 days (SD = 87) for subjects to reach the dose at which clozapine response was achieved. Once this dose was reached, the average response time was 17 days (SD = 14, range = 2-56). All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation. No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks (SD = 50). CONCLUSIONS: In this study, all patients who responded to clozapine did so within 8 weeks of a change in dose. Thus, there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen.

Adult↗
PubMed1996

The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse.

Drug abuse is common in schizophrenia. Previous studies suggested patients with the deficit syndrome have a lower risk of drug abuse than do patients without deficit features. We distinguished deficit and nondeficit groups in the DSM-IV Field Trial dataset, and compared the two groups relative to current and lifetime (worst ever) severity of alcohol, cannabis, and other drugs of abuse. Deficit syndrome patients had a lower severity of current use of alcohol and other drugs, but the two groups did not differ significantly relative to cannabis use. Deficit patients also had less severe lifetime use of all three classes of drugs. These findings could not be attributed to differences between the deficit and nondeficit groups in demographics, severity of psychotic symptoms, chronicity of illness, or the quality of information available for the two groups. Deficit categorization and drug abuse were independently associated with poor level of function. Negative symptoms broadly defined were weaker predictors of drug abuse than was the deficit/nondeficit categorization. These findings further support the validity of the deficit syndrome of schizophrenia. Within schizophrenia, groups with relatively high or low risk for substance abuse can be identified.

Adult↗
PubMed1996

Clozapine conflict.

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Antipsychotic Agents↗