PubMed Health⌕ Search

Biomedical subjects

B D Marshall

Publications and source records attributed to B D Marshall.

At least 19 recordsLinked to original sources

Risperidone versus haloperidol on secondary memory: can newer medications aid learning?

The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies.

Adult↗

Risperidone in treatment-refractory schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. METHOD: Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. RESULTS: Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. CONCLUSIONS: Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.

Adult↗

Risperidone vs. haloperidol on reaction time, manual dexterity, and motor learning in treatment-resistant schizophrenia patients.

BACKGROUND: The present study compared the effects of risperidone vs. haloperidol on reaction time, manual dexterity, and two types of motor learning in a sample of treatment-resistant schizophrenia patients. METHODS: Fifty-six DSM-III-R diagnosed schizophrenia inpatients participated in a randomized, double-blind comparison of risperidone vs. haloperidol. Measures of reaction time, manual dexterity, motor sequence learning, and gross motor learning were administered at baseline, after 4 weeks of fixed-dose medication, and after 4 weeks of flexible-dose medication. RESULTS: The results indicated that patients receiving risperidone showed greater improvement in reaction time and manual dexterity than patients receiving haloperidol. After covarying symptom changes and movement disorder ratings, the results remained significant. The two treatment groups did not differ on either measure of motor learning. CONCLUSIONS: The differences in performance in reaction time and manual dexterity may be due to a specific beneficial effect of risperidone, as opposed to a general reduction in extrapyramidal symptom liability, compared to haloperidol.

Adult↗

Risperidone versus haloperidol for perception of emotion in treatment-resistant schizophrenia: preliminary findings.

Currently, little is known about the pharmacological effects of the new generation of antipsychotic medications on perception of emotion in schizophrenia. The present study was designed to compare the effects of risperidone versus haloperidol on the ability to perceive emotion in 20 treatment-resistant schizophrenia patients, using a double-blind design. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception test (brief interpersonal vignettes presented on videotape). These measures were administered during the final week of baseline and after 8 weeks of double-blind medication. Risperidone treatment produced a greater effect on patients' ability to perceive emotion compared with haloperidol treatment. Additionally, all patients who received risperidone demonstrated improvement in performance between baseline and retest, compared with four of the nine patients who received haloperidol. When changes in positive symptoms were statistically controlled, the results remained significant. These findings suggest that resperidone may facilitate patients' ability to accurately perceive emotion, an effect which may be mediated either directly by risperidone's pharmacological action or perhaps indirectly by its influence on basic neurocognition.

Adult↗

Does risperidone improve verbal working memory in treatment-resistant schizophrenia?

OBJECTIVE: Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on verbal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation. METHOD: Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy. RESULTS: Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible dose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory performance. CONCLUSIONS: Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities.

Adult↗

Simultaneous determination of plasma haloperidol and its metabolite reduced haloperidol by liquid chromatography with electrochemical detection. Plasma levels in schizophrenic patients treated with oral or intramuscular depot haloperidol.

A simple and highly sensitive liquid chromatographic method with electrochemical detection for the simultaneous determination of haloperidol and its metabolite reduced haloperidol in human plasma has been developed. The sample preparation for the analysis involves a simple one-step extraction procedure with 10% methylene chloride in pentane. The compounds were separated on a cyano column maintained at a temperature of 40 degrees C and were detected electrochemically by a flow-through analytical cell kept at +0.95 V. The standard curve is linear over the range of 0.1 to 15 ng/ml and the lower limit of quantitation is 0.1 ng/ml for haloperidol and 0.25 ng/ml for reduced haloperidol which is equivalent to approximately 40 pg on column when 1 ml of plasma was used for the analysis. The lower limit of quantitation for reduced haloperidol can be extended to 0.1 ng/ml if 2 ml of plasma is used in the analysis. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%. Commonly co-administered drugs and other neuroleptics used in conjunction with haloperidol did not interfere in the determination of either haloperidol or reduced haloperidol. This method has been successfully used for the determination of haloperidol and reduced haloperidol in plasma and their levels in patients treated with various doses oral haloperidol or intramuscular haloperidol decanoate are reported.

Administration, Oral↗

Optimal drug and behavior therapy for treatment-refractory schizophrenic patients.

Thirteen treatment-refractory schizophrenic patients (10 men and three women) who were receiving more than 50 mg/day of haloperidol and who had been hospitalized for more than 1 year successfully tolerated a mean dose reduction of 63% with consequent improvement in psychopathology and side effects. The addition of intensive behavior therapy to the optimal dose of haloperidol yielded further improvements in functional behavior, such as self-care and social interaction.

Adult↗

Impact of clinical pharmacokinetics on neuroleptic therapy in patients with schizophrenia.

This review covers some recent work on: 1. The effects of route of administration on the pharmacokinetics of fluphenazine and some of its metabolites; 2. The clinical pharmacokinetics of fluphenazine in acute patients medicated with oral fluphenazine; 3. The clinical pharmacokinetics of haloperidol in acute patients medicated with oral haloperidol; 4. The clinical pharmacokinetics of fluphenazine in the maintenance of individuals with chronic schizophrenia with fluphenazine decanoate; 5. A systematic dose reduction study in maintenance treatment refractory patients with oral haloperidol. A study in which plasma levels of fluphenazine and fluphenazine sulfoxide were measured in a group of DSM-III-R patients with schizophrenia before and after switching from oral fluphenazine to depot fluphenazine, decanoate revealed much higher levels of fluphenazine sulfoxide with oral medication compared with those found with depot fluphenazine. These data illustrate the effect of "first pass" metabolism after oral fluphenazine. Thus in a group of 33 patients randomly assigned to receive 5 mg, 10 mg or 25 mg oral fluphenazine daily, steady state plasma fluphenazine levels at each dose were significantly lower that those of fluphenazine sulfoxide or 7-hydroxy-fluphenazine, although there were no significant differences between the levels of fluphenazine and fluphenazine N4-oxide. On the other hand, plasma levels of the parent drug were significantly higher than those of any metabolite in a corresponding group of patients at steady state on depot medication. These observations underscore the importance of route dependent differences in the pharmacokinetics of fluphenazine which can lead to problems when switching patients from oral to depot neuroleptics. The concept of "disabling side-effects" is an important development in understanding relationships between plasma levels of neuroleptic drugs and clinical response in patients with schizophrenia. Risk-benefit analysis shows clearly that evaluation of relationships between plasma levels and clinical response must take into account the consequences of side-effects which the patient feels have a negating effect on therapy. Emerging data on putative therapeutic plasma level ranges in maintenance therapy are potentially important and may be particularly useful in the maintenance of patients on low dose therapy. It is noteworthy that in a carefully executed dose reduction study in treatment resistant patients under medication with haloperidol, the mean lowest effective dose (8.7 ng/mL) lay within the optimal therapeutic range (5 ng/mL to 12 ng/mL) found in acutely psychotic patients. The study showed that gradual dose reduction of neuroleptic was possible in chronic treatment resistant patients with schizophrenia who were originally thought by ward staff to require high doses of neuroleptic.(ABSTRACT TRUNCATED AT 400 WORDS)

Antipsychotic Agents↗

Prediction of response to haloperidol dose reduction by Span of Apprehension measures for treatment-refractory schizophrenic patients.

Thirteen treatment-refractory schizophrenic patients participated in a haloperidol reduction study. Two of the subjects were unable to tolerate medication reduction. These subjects were comparable to the other patients in terms of initial clinical variables but were outliers on baseline accuracy and reaction time measures from the Span of Apprehension. The results suggest that aspects of basic visual processing and motor response speed may identify patients who require higher neuroleptic doses.

Adult↗

Systematic dosage reduction in treatment-resistant schizophrenic patients.

Thirteen treatment-resistant, chronically institutionalized schizophrenic patients on high-dose neuroleptic (the equivalent of at least 50 mg of haloperidol (HPL) daily) were transferred to a special research ward for a trial of systematic dosage reduction. In these 13 patients, it was possible to reduce the dose of HPL from 63.1 mg/day (SD +/- 12.5, range = 50-80 mg/day) to 23.1 mg/day (SD +/- 16.3, range = 0-65 mg/day) over a mean period of 32 weeks (SD +/- 9.6, range = 15-46 weeks). Their total Brief Psychiatric Rating Scale (BPRS) scores were improved (p = .04), they definitely experienced fewer extrapyramidal side effects (p = .01), and 6 of the patients showed global improvement. On several behavioral rating scales there was, if anything, an improvement in negativistic behavior. The substantial dosage reduction was paralleled by a comparable drop in plasma levels. HPL plasma levels at baseline were 38.8 ng/mL (SD +/- 17.8, range = 21.5-69.5 ng/mL) and at the lowest effective dose were 12.4 ng/mL (SD +/- 10.3, range = 0-43.4 ng/mL).

Adult↗

Optimal drug and behavior therapy for treatment-refractory institutionalized schizophrenics.

Institutionalized persons with a deteriorating form of schizophrenia that was refractory to neuroleptic medication were titrated downward in their haloperidol dose. Based on ratings of their clinical status, an optimal dose was reached that was an average 66 percent reduction from their initial levels. Patients then participated in a personalized, intensive behavior therapy program to remediate their extreme, persisting deficits and disturbances in behavior.

Adult↗

Successful behavioral treatment of polydipsia in a schizophrenic patient.

Behavioral treatment of a 35 year old female with chronic schizophrenia and water intoxication with seizures was conducted on an inpatient psychiatric unit. Treatment included frequent daily weights, restricted fluid intake, positive reinforcement for program compliance, and time-out from reinforcement following significant weight gain or other specified program violations. The final 6 months of the 30 month treatment program were a maintenance phase during which most contingencies were faded and all fluid restrictions were removed. There was no reported recurrence of polydipsia after 18 months of community placement.

Adult↗

Effects of fenfluramine on neuropsychological and communicative functioning in treatment-refractory schizophrenic patients.

Reported behavioral improvement among autistic patients following feufluramine treatment and a high serotonin level among certain chronic schizophrenic patients suggested that fenfluramine treatment might be beneficial with such schizophrenic patients, especially within the realm of neuropsychological and communicative functioning. A brief neuropsychological battery was administered to eight chronic schizophrenic subjects before, during, and after fenfluramine treatment. Conversations in controlled settings were audiotaped before and during fenfluramine treatment for seven of these subjects and one additional subject. These language samples were analyzed for communicative competence and evidence of thought disorder. Overall, neuropsychological and communicative functioning was worse under the fenfluramine condition, even though blood serotonin levels were about half those at baseline conditions. The results suggest that it is not the higher levels of blood serotonin by themselves that are related to depressed neuropsychological, communicative, and other functioning. In fact, the higher levels of serotonin may well be related to adaptations for maximal level of functioning. These results suggest caution in the use of fenfluramine for other schizophrenic populations.

Adult↗

Adverse effects of fenfluramine in treatment refractory schizophrenia.

Fenfluramine was administered to eight severely ill schizophrenic patients as an adjunct to neuroleptic drugs in a double-blind, multiple baseline design. A significant adverse effect of fenfluramine on psychopathology was detected through nurses' ratings, target symptom scales, the Brief Psychiatric Rating Scale, and time-sampled behavioral observations. Clinical deterioration was correlated with fenfluramine-induced reductions in blood serotonin levels and persisted beyond the point of discontinuation of fenfluramine.

Adult↗

An early record of Culicoides species (Diptera: Ceratopogonidae) developing in the dung of game animals in southern Africa.

The value of the dung of game animals as a larval habitat for Culicoides species was briefly investigated in 1973/74 in the Kruger National Park, Transvaal, Republic of South Africa. A total of 4 species in the subgenus Avaritia was reared, 3 from elephant dung, 2 from zebra dung and 1 from the dung of buffalo. These early studies have recently led to more intensive rearing and a better understanding of the systematics of this subgenus in the Afrotropical region.

Animals↗