Level of haloperidol in plasma is related to electroencephalographic findings in patients who improve

doi:10.1016/0165-1781(92)90077-G

Psychiatry Research

Volume 42, Issue 2, May 1992, Pages 129-144

https://doi.org/10.1016/0165-1781(92)90077-G Get rights and content

Abstract

This study analyzed interrelationships among plasma level of haloperidol (HAL), electroencephalographic (EEG) changes, and clinical response in 37 acutely exacerbated schizophrenic patients after a 6-week period of treatment. Two hypotheses were tested: (1) EEG theta response to HAL depends on levels of HAL in plasma, and this relationship is expressed in patients showing a clear clinical response (responders). (2) Responders and nonresponders are characterized by a different neuroleptic EEG profile. EEG examinations (resting, waking EEG) were performed at study entry, end point of the placebo period (“baseline”), and weekly during the entire HAL treatment period. EEG response was measured by power spectral changes in four frequency bands (delta, theta, alpha, and beta); clinical response was assessed by the Brief Psychiatric Rating Scale. There was a significant relationship between HAL plasma levels and EEG theta activity for treatment responders, whereas no relationship was detected for the nonresponders. Furthermore, there were EEG changes (in the delta and alpha bands) that depended on clinical response but did not show any relationship, either in responders or nonresponders, to HAL plasma levels. These results supported both hypotheses.

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A literature review was conducted to ascertain whether or not EEG spectral abnormalities are consistent enough to warrant additional effort towards developing them into a clinical diagnostic test for schizophrenia.
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The present study examined the stability of the density and distribution of MEG slow waves during three conditions—rest, mental arithmetic and imagery—in 30 schizophrenic patients and 17 healthy controls. Schizophrenic patients displayed a higher density of delta and theta generators primarily in temporal and parietal areas. The group difference was not affected by the particular conditions. The focal concentration of delta and theta slow waves did not differ between patients with and without neuroleptic medication, whereas the prominence of theta dipoles in the temporal area correlated with neuroleptic dosage. The relative amount of temporal slow waves was correlated with the negative symptoms score (PANSS-N) suggesting that temporal dysfunction may be related to negative symptomatology.
Results suggest that the distribution of slow-wave activity, measured in a standardized setting, might add diagnostic information about brain abnormalities in schizophrenia.
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To determine whether two groups of schizophrenic patients representing the two extremes of the neuroleptic response-spectrum (consistent responders vs. consistent nonresponders) differ with respect to their neuropsychological profile. Neuroleptic-responder (R; n=36) and -nonresponder (NR; n=39) schizophrenic patients were recruited according to a priori defined criteria of responsiveness to typical neuroleptics. Seven neuropsychological domains were assessed and compared between groups: attention-vigilance, abstraction-flexibility, spatial organization, visual-motor processing, visual memory, verbal abilities, and verbal memory and learning. All measures were standardized using the scores of 36 healthy volunteers. NR schizophrenic patients performed worse in all neuropsychological domains compared to normal controls and R schizophrenic patients. However, only performances on visual memory, verbal abilities, and verbal memory and learning were significantly poorer in NR compared to R patients. Only the latter domain significantly differentiated NR patients from the other two groups. R patients performed at an intermediate level in all domains. This report of differences in neuropsychological profile between neuroleptic-responder and -nonresponder schizophrenic patients adds to the growing evidence supporting the value of distinguishing schizophrenic patients on the basis of their therapeutic response to neuroleptics.
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Citation Excerpt :
The various effects of neuroleptic medication on the human EEG/MEG present a problem in the interpretation of data of any study like ours. General slowing of EEG frequencies has been reported as a consequence of neuroleptic medication (Koshino et al 1993; Malow et al 1994) or, more specifically, increased theta activity concomitant with an increase in haloperidol plasma levels has been reported in patients who responded to the treatment (Czobor and Volavka 1992). Nonetheless, other studies described the effects of medication as normalizing (e.g., Canive et al 1996, 1998; Saletu et al 1990, 1994).
Background: Schizophrenic patients exhibit more activity in the electroencephalographic delta and theta frequency range than do control subjects. Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in the magnetoencephalogram (MEG), the distribution of its sources, and associations between symptom profiles and sources of low-frequency activity in the brain.
Methods: Whole-head MEG recordings were obtained from 28 schizophrenic patients and 20 healthy control subjects during a resting condition. The generators of the focal magnetic slow waves were located employing a single moving dipole model. Distributed or multiple delta and theta sources were captured by the minimum norm estimate.
Results: Both localization procedures showed slow wave activity to be enhanced in schizophrenic patients compared with control subjects. Focal slow wave activity differed most between groups in frontotemporal and in posterior regions. Slow wave activity was associated with symptom characteristics in that positive symptoms varied with frontal delta and theta activity.
Conclusions: Results indicate that activity in low-frequency bands in schizophrenic patients exceeds the activity of control subjects in distinct areas, and that this focal clustering of neuromagnetic slow waves may be related to psychopathologic characteristics.
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Topographic quantitative electroencephalographic (EEG) power and frequency indices were collected in 17 treatment refractory, DSM-III diagnosed schizophrenic patients, before and after acute (single dose) and chronic (six weeks) clozapine treatment, as well as in 17 healthy volunteers. Prior to treatment, patients exhibited greater overall absolute theta power, slower mean alpha frequency and elevated absolute delta and total power in anterior regions. Acute dosing increased total spectrum power globally, slow wave power posteriorally, mean alpha frequency and beta power anteriorally and decreased alpha power posteriorally. Six weeks of clozapine treatment significantly reduced clinical ratings of positive and negative symptoms as well as symptoms of global psychopathology. Chronic treatment resulted in EEG slowing as shown by decreases in relative alpha power, mean beta/total spectrum frequency and by widespread increases in absolute total and delta/theta power. The preliminary findings suggest that brain electric profiling may be a promising tool for assessing and understanding the central impact of pharmacotherapeutic interventions in schizophrenia.
Electroencephalography in schizophrenic patients: Comparison between neuroleptic-naive state and after treatment
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Electroencephalography of 12 schizophrenic patients was recorded in a neuroleptic-naive state and after 6.2 ± 1.1 months of treatment, when they were on medication and in partial remission. Compared with age- and sex-matched controls, the neuroleptic-naive schizophrenics had less alpha 2 power. In the medicated state, alpha 2 power and slow-wave power were reduced as compared with the neuroleptic-naive state. The reduction in alpha 2 power may occur from the early stage of the disease and progress even though the patients are medicated and clinically improved.

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^☆: An earlier version of this report was presented at the Symposium of the International Pharmaco-EEG Group, Gothenburg, Sweden, June 30, 1990.

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Level of haloperidol in plasma is related to electroencephalographic findings in patients who improve☆

Abstract

Biological Psychiatry

European Journal of Pharmacology

European Neuropsychopharmacology

Electroencephalography and Clinical Neurophysiology

Trends in Neuroscience

European Neuropsychopharmacology

Schizophrenia Research

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Biological Psychiatry

DSM-III: Diagnostic and Statistical Manual of Mental Disorders

On the methods and theory of reliability

Journal of Nervous and Mental Disease

Elektroenzephalographie und psychiatrische pharmacotherapie

Vigilance and evaluation of psychotropic drug effects on EEG

Pharmakopsychiatry

Functional and anatomical brain imaging: Impact on schizophrenia research

Schizophrenia Bulletin

Plasma homovanillic acid as a predictor of response to neuroleptics

Archives of General Psychiatry

Use of the Research Diagnostic Criteria and the Schedule for Affective Disorders

American Journal of Psychiatry

Quantitative EEG analysis of high-dosage haloperidol effects in therapy resistant schizophrenic patients

EEG and human psychopharmacology

Annual Review of Pharmacology and Toxicology

EEG profiles and bioavailability measures of psychoactive drugs

Development and critical evaluation of an objective procedure for the electroencephalographic classification of psychotropic drugs

Development of a classification rule for four clinical therapeutic psychotropic drug classess with EEG power spectrum variables of human volunteers

Pharmakopsychiatry

A simple sequentially rejective multiple test procedure

Scandinavian Journal of Statistics

Interet pronostique de l'EEG au cours de l'evolution des schizophrenes

Electroencephalography and Clinical Neurophysiology

Electroencephalography and pharmacopsychiatry

Qualitative and quantitative EEG findings in schizophrenia

Schizophrenia Bulletin

Digital computer analyzed sleep and resting EEG during haloperidol treatment

American Journal of Psychiatry

CEEG and dynamic brain mapping in the bioavailability and bioequivalence of psychotropic drugs

Computerized EEG: Predictor of outcome in schizophrenia

Journal of Nervous and Mental Disease