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Biomedical subjects

W T Carpenter

Publications and source records attributed to W T Carpenter.

At least 55 records · Page 3Linked to original sources
PubMed1996

Maintenance therapy of persons with schizophrenia.

Developments over the past 20 years in maintenance treatment have substantially reduced problems with relapses, rehospitalization, and serious psychopathology and dysfunction for most patients with schizophrenia. Therapeutic gains can be accomplished with minimal dosing strategies, targeted drug therapy for medication-refusing patients, psychosocial interventions, and new drugs. Although minimal dose maintenance requires close clinical monitoring and effective collaboration, this strategy reduces side effects and negative symptoms and may thereby translate into greater medication compliance. Psychosocial therapeutics that include family intervention in conjunction with antipsychotic drug treatment reduce relapse rates, but further study is needed. Lithium, carbamazepine, benzodiazepines, beta-blockers, and antidepressant drugs along with electroconvulsive therapy and social skills training provide other relevant approaches in maintenance treatment. Before a maintenance role for new drugs such as clozapine and risperidone is clarified, controlled studies are needed. However, the advantages with motor side effects and secondary negative symptoms should enhance clinical course and medication compliance, and superior antipsychotic prophylaxis is hypothesized. Special issues in maintenance treatment include difficulty in predicting relapse, increased risk of adverse drug effects in elderly patients, and complication of the nonpsychotic aspects of schizophrenia by continued use of antipsychotic drugs. Optimal maintenance treatment incorporates early detection and outpatient management of symptom exacerbation, minimal dosing to increase compliance and reduce adverse effects, psychosocial intervention to reduce relapse rates and enhance functioning, and the integration of several therapeutic modalities and the provision of case managers and assertive community treatment teams.

Ambulatory Care↗
PubMed1995

Borna disease virus and schizophrenia.

The development of a new serological assay method to detect antibodies in human sera recognizing Borna disease virus (BDV) proteins and a clinical pilot study are presented. Psychiatric patients from a schizophrenia research clinic in Baltimore, Maryland, were examined for antibodies to BDV antigen with traditional indirect immunofluorescence assays (IFA) that used both single and double labeling techniques and also with a Western blot assay capable of detecting antibodies to the three BDV proteins from a human neuroblastoma cell line. Thirteen of 90 (14.4%) patients and 0/20 control subjects had antibodies that recognized more than one BDV protein on the Western blot. Three patients had antibodies that recognized all three BDV proteins. Magnetic resonance imaging assessments of the volume of the putamen (with controls for total cranial volume) differentiated BDV+ from BDV- patients, and there were trend differences for bilateral amygdalae and the left amygdala-hippocampal process. We conclude that: (1) the Western blot assay is superior to IFA assays in BDV serology studies, (2) detection of antibodies to more than one BDV protein is a useful working criterion for seropositivity, (3) the 14.5 kDa BDV protein is 10 times more predictive of seropositivity than either the 38/40 kDa or the 24 kDa protein, (4) there is tentative evidence for a schizophrenia-control difference in the prevalence of anti-BDV antibodies, and (5) it is likely that there are neuroanatomical/behavioral features that differentiate seropositive from seronegative schizophrenic patients.

Adult↗
PubMed1995

Prodromal symptoms vs. early warning signs and clinical action in schizophrenia.

The term "prodromal symptoms" has traditionally referred to prepsychotic changes in thought, affect, and cognition that precede the initial onset of schizophrenia. Recently, however, the term has been extended into a clinical action context to refer to the early warning signs (EWS) of impending relapse in patients already diagnosed as having schizophrenia. However, recent reports reviewed by Norman and Malla (1995, this issue) use a narrow definition of prodromal symptoms and question their use in the clinical action context. We argue that the dual use of the term "prodromal symptoms" has led to conceptual confusion and to the impression that EWS cannot be used effectively for clinical action. The ability to base clinical action on EWS is central to schizophrenia therapeutics and is the cornerstone of pharmacological strategies based on early intervention. Our review of the evidence suggests that the effective clinical use of EWS depends on (1) the inclusion of both psychotic and nonpsychotic symptoms as EWS; (2) the use of clinician judgment in combination with predefined symptom changes to define the occurrence of EWS; (3) frequent clinical visits; and (4) the use of family or caregiver informants. We therefore suggest that, in the clinical action context, the terminology "early warning signs of impending relapse" should be used instead.

Anti-Anxiety Agents↗
PubMed1995

Treatment outcomes in schizophrenia: implications for practice, policy, and research.

Outcomes research on treatments for schizophrenia has identified a number of efficacious interventions. The degree to which such scientific knowledge influences the care delivered in everyday practice depends on a large number of patient, practitioner, service system, and other social factors. The current atmosphere for change in the health care delivery system poses both risks and opportunities to improve care for persons with this disorder. Scientific knowledge about treatment outcomes must inform this rapid evolution of practice, policy, and research to ensure that effective treatments are preserved and available for all who need them and that new treatments continue to be developed, evaluated, and disseminated.

Combined Modality Therapy↗
PubMed1995

Serotonin-dopamine antagonists and treatment of negative symptoms.

This review aims to examine the basis of the hypothesis that simultaneously modifying serotonergic and dopaminergic neurotransmission is effective in schizophrenia and to assess critically clinical efficacy data with respect to negative symptoms. A variety of serotonin and dopamine agonists can induce psychosis, so it is to be expected that certain serotonin and dopamine antagonists could have antipsychotic effects. It is known that serotonergic afferent neurons synapsing with dopaminergic neurons exert an inhibitory effect. Because hypodopaminergic pathophysiology has been postulated as being responsible for negative symptoms, serotonin antagonists may be therapeutic. A number of clinical trials provide data on the effect of adding serotonergic drugs to conventional neuroleptics in the treatment of schizophrenia, and there are now studies with drugs that combine serotonin and dopamine antagonism in the same molecule. There may be a modest enhancement of the antipsychotic effect of antagonism at postsynaptic dopamine D2 receptors. The effects of serotonin antagonism on negative symptoms are, however, more encouraging, although the issue is complicated because methodologic difficulties confound the interpretation of the results of these studies. The weight of the evidence suggests that negative symptoms improve when the treatment of schizophrenia includes drugs that diminish serotonergic activity. However, this may be because of indirect effects, such as an enhanced antipsychotic action, diminished extrapyramidal side effects, increased activation, or decreased depression--all features associated with secondary negative symptoms. The challenge is to address primary negative symptoms, and this has been attempted in a small number of patients; the results are not very encouraging.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipsychotic Agents↗
PubMed1995

Patient response and resource management: another view of clozapine treatment of schizophrenia.

OBJECTIVE: Issues in clozapine treatment were considered in terms of implications for resource management. METHOD: A critical review of the literature on time course and pattern of response to clozapine was used to address treatment of negative symptoms, late responders, and extent of clinical benefit in ordinary settings. RESULTS: Superior efficacy of clozapine for partial and poor neuroleptic responders is observed in about one-half of the cases. Response is rapid once a therapeutic dose is reached, and the data do not support the proposition that some patients first respond only after 3-12 months of therapy. The cumulative benefit over several months of treatment and the broad range of symptoms involved in response are similar to those for typical neuroleptic drugs, suggesting that clozapine's superiority is based on greater effectiveness rather than a unique profile of treatment effects. Clozapine appears to be effective for secondary, but not primary, negative symptoms. Modal response is moderate, and extensive rehabilitation and clinical services are required to substantially enhance functional outcome. CONCLUSIONS: Many more patients merit trials with clozapine. Economic costs and adverse drug effects can be minimized by selecting patients most likely to benefit and discontinuing clozapine treatment when benefit is not observed within 2-4 months. Appropriate patients include 1) those with good responses to typical neuroleptics who experience substantial adverse effects and 2) those whose disorders respond poorly to standard neuroleptics and are defined by psychotic symptoms, thought disorder, and hostility. Treatment of primary negative symptoms is not supported by the current experimental data.

Antipsychotic Agents↗
PubMed1995

New diagnostic issues in schizophrenic disorders.

The evolution of our understanding of schizophrenia has provided new concepts that substantially alter answers to questions such as age of onset, distribution by sex, and treatment response. Moreover, these new concepts offer heuristic advantages in etiopathophysiological study designs and permit investigators to address key sources of artifact. We discuss the unitary versus the clinical syndromal concept of schizophrenia and describe the implications of the latter with regard to the study of schizophrenia. We also present a heuristic tripartite division of schizophrenic symptoms for reducing syndromal heterogeneity.

Age of Onset↗
PubMed1994

Schizophrenia.

Explore the source record for details and available documents.

Humans↗
PubMed1994

Neuropsychological impairments in deficit vs nondeficit forms of schizophrenia.

BACKGROUND: Previous studies have suggested that functional impairments of the frontal and parietal lobes are related to the deficit symptoms of schizophrenia. The purpose of the current study was to examine whether neuropsychological measures of frontal and parietal lobe function differentiated deficit from nondeficit patients. Neuropsychological measures of temporal lobe function were used as contrast measures. METHODS: The performance of 18 deficit and 21 nondeficit schizophrenic patients was examined on neuropsychological measures of executive, visuospatial, and memory functions, selected on the basis of their association with lesions of either the frontal, parietal, or temporal lobes. The results from the schizophrenic subgroups were compared with the results on the same measures obtained from 30 normal controls. RESULTS: Deficit patients performed more poorly than nondeficit patients on two frontal lobe measures, the Stroop Color-Word Interference and Trails Making B tests, and one parietal lobe measure, the Mooney Faces Closure Test. There were no differences in performance on the temporal lobe measures between the two groups. Both groups performed more poorly on the tests than the normal controls. CONCLUSIONS: The results suggest that deficit patients may have greater performance impairments on neuropsychological measures associated with frontal and parietal neuropsychological abnormalities.

Adult↗
PubMed1994

Depressive symptoms and the deficit syndrome of schizophrenia.

One of the most influential ideas in schizophrenia research is that schizophrenia may be a syndrome with significant pathophysiological heterogeneity, rather than a single disease. Among patients with schizophrenia, presence or absence of the deficit syndrome has been suggested as a method for defining relatively homogeneous groups. The criteria for the deficit syndrome require the presence of negative symptoms that are judged primary to the illness, rather than to factors, such as depressive mood, that may resemble the negative symptoms of schizophrenia. To test one aspect of the validity of the primary/secondary judgment, we tested the relationship of depressive symptoms to the deficit/nondeficit categorization. Using independent clinician ratings, the depressive mood of deficit and nondeficit patients was compared at the time the categorization was made, and at an average follow-up of 2 1/2 years. Using patients' self ratings, deficit and nondeficit patients were compared at an average follow-up of 1 1/2 years. Deficit patients had significantly less severe depressive symptoms by clinicians' ratings both cross-sectionally and at follow-up, and less severe self-rated symptoms at follow-up. These differences were not due to confounding by age, race, sex, socioeconomic status, or chronicity. These results support the validity of the deficit/nondeficit categorization.

Adult↗
PubMed1994

Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia.

OBJECTIVE: Clozapine is an atypical neuroleptic with superior efficacy in severely ill, treatment-resistant inpatients with schizophrenia. To determine if clozapine's differential efficacy generalizes to less ill, outpatients populations, the authors examined the effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. METHOD: Outpatients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospective 6-week trial of fluphenazine participated in a 10-week, double-blind, parallel-groups comparison of clozapine and haloperidol. Thirteen men and six women were given clozapine, and 15 men and five women were given haloperidol. Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed. Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day (SD = 45.8) and 24.8 mg/day (SD = 5.5), respectively. RESULTS: Clozapine was superior to haloperidol for treating positive symptoms. In addition, eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria. Clozapine was also superior to haloperidol for treating negative symptoms, although these effects were relatively minor. Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia. Overall, clozapine was well tolerated. CONCLUSIONS: Clozapine has superior efficacy for treating positive symptoms in partially responsive outpatients with chronic schizophrenia, suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill.

Adult↗
PubMed1994

Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia.

The manifest clinical heterogeneity of schizophrenia, combined with the failure, to date, to demonstrate the existence of a unitary disease process, has led to the conceptualization of schizophrenia as a pathophysiologically heterogeneous disorder. Various approaches have been developed to define homogeneous subgroups of schizophrenic patients. An alternative approach to the use of multiple criteria for defining putative disease entities is the use of specific sign and symptom complexes, or domains of psychopathology, for reducing heterogeneity. There is now considerable evidence supporting the separation of schizophrenic symptoms into three domains: hallucinations and delusions, thought disorder, and deficit symptoms. The conceptual evolution and validating evidence for this approach are reviewed, and an illustration of how the domains of psychopathology are applied in schizophrenia research is presented.

Brain↗
PubMed1993

Strong inference, theory testing, and the neuroanatomy of schizophrenia.

Failure to address the putative etiologic and pathophysiologic heterogeneity of the schizophrenia syndrome and problems in definitive assessment of human brain function have impaired progress in schizophrenia research. New approaches to psychopathology and converging evidence from antemortem and postmortem study can now result in more decisive study of the neuroanatomy and neuropathology of schizophrenia.

Brain↗
PubMed1993

Case identification and stability of the deficit syndrome of schizophrenia.

In certain situations, such as large epidemiological studies, it may be necessary to use proxy case-identification tools instead of "gold-standard" assessments. The deficit syndrome of schizophrenia requires a clinical assessment that may not be feasible in some study populations. Measures for the discrimination of deficit and nondeficit patients, based on the Brief Psychiatric Rating Scale (BPRS), were assessed in a group of 100 outpatients with chronic schizophrenia. A rationally based case-identification tool was validated, and its case-identification properties were found to be stable over time; consequently, this proxy measure may be of use in other data sets. The stability of the relationship between this BPRS measure and the deficit/nondeficit categorization supports the view that it is a valid categorization.

Adult↗