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Biomedical subjects

R D Weiner

Publications and source records attributed to R D Weiner.

At least 19 recordsLinked to original sources
PubMed1999

EEG correlates of the response to ECT: a possible antidepressant role of brain-derived neurotrophic factor.

Studies on the relationship of electroencephalographic (EEG) data to the therapeutic response to electroconvulsive therapy (ECT) have been carried out since the 1940s, but for many years they did not yield any consistent correlates. Recent studies, however, are providing a growing body of evidence of relationships between the antidepressant response to ECT and both the ictal (recorded during ECT seizures) and interictal (recorded during waking) EEG. These studies appear to be consistent in pointing to the importance of electrophysiologic changes in the prefrontal cortex as a potential mediator of the antidepressant response to ECT. The available findings are reviewed and discussed in light of recent neurophysiologic and neuropsychiatric research, including that related to neurotrophic factors.

Depressive Disorder↗
PubMed1998

Changes in seizure threshold over the course of electroconvulsive therapy affect therapeutic response and are detected by ictal EEG ratings.

Therapeutic effectiveness of electroconvulsive therapy is influenced by the degree to which the stimulus intensity exceeds the seizure threshold. However, the threshold rises variably over the treatment course, confounding maintenance of desired relative stimulus intensity. In 47 depressed patients, decreases in relative stimulus intensity between treatments 1 and 6 were associated with diminished therapeutic response at treatment 6 for unilateral (UL) ECT. A multivariate model including manual ratings of ictal EEG data predicted whether seizure threshold rose with 82% accuracy. The same EEG variables were also significantly related to therapeutic response. Thus, decreases in relative stimulus intensity over the ECT course affect the therapeutic potency of UL ECT. Further, ictal EEG indices have considerable potential for predicting such stimulus intensity changes and their effect on therapeutic outcome.

Aged↗
PubMed1998

The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient.

Many patients who receive electroconvulsive therapy (ECT) are benzodiazepine dependent or are anxious and require benzodiazepine drugs. Because these agents may diminish the therapeutic effectiveness of ECT, we explored the dosing, safety, and efficacy of pre-ECT flumazenil administration, a benzodiazepine-competitive antagonist, in patients receiving benzodiazepine medications. We report our experience with 35 patients who received both flumazenil and benzodiazepine drugs during their ECT course. We compared seizure duration with and without flumazenil and compared treatment efficacy to 49 patients who received ECT without either of these medications. Flumazenil could be safely administered with ECT. A few subjects taking higher chronic benzodiazepine dosages experienced breakthrough anxiety or withdrawal symptoms, which were well managed by dosing flumazenil immediately before the anesthetic agent and by immediate posttreatment benzodiazepine administration. A dose of 0.4-0.5 mg was adequate for all but those taking the highest benzodiazepine dosages, where 0.8-1.0 mg resulted in a clinically more effective reversal. No differences in efficacy or seizure duration were found as a function of flumazenil administration. Flumazenil offers the promise of safe and effective ECT in patients receiving benzodiazepine drugs. Follow-up outcome investigation on a random assignment basis will be necessary for definitive assessment of the value of flumazenil. In addition, the direct effect of benzodiazepine drugs and the flumazenil/benzodiazepine combination on ECT seizures remains to be determined.

Adult↗
PubMed1997

Clozapine-induced electroencephalogram changes as a function of clozapine serum levels.

Specific electroencephalogram (EEG) changes during clozapine therapy were prospectively studied in a cohort of 50 chronic state hospital patients with schizophrenia who were randomly assigned to one of three nonoverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL, and 350-450 ng/mL). EEGs were obtained before clozapine was instituted, and after 10 weeks of treatment. Fifty-three percent of patients showed EEG changes during the 10-week study period. We observed three seizures (6%), one in a patient on 900 mg (serum level 320 ng/mL) clozapine, and two in patients with lower clozapine serum levels (200-300 ng/mL) who had prior histories of seizures and inadequate valproate coverage. Thirteen percent of patients developed spikes with no relationship to dose or serum level of clozapine. Fifty-three percent of patients developed slowing on EEG. Compared to plasma levels below 300 ng/mL, a clozapine serum level between 350 and 450 ng/mL led to more frequent and more severe slowing. The EEG slowing correlated with observed sleepiness, although this factor was not sufficient to explain the severity of high-dose effects.

Adult↗
PubMed1997

The largest Lyapunov exponent of the EEG during ECT seizures as a measure of ECT seizure adequacy.

Attributes of the electroencephalogram (EEG) recorded during electroconvulsive therapy (ECT) seizures appear promising for decreasing the uncertainty that exists about how to define a therapeutically adequate seizure. In the present report we study whether one promising and not yet tested ictal EEG measure, the largest Lyapunov exponent (lambda1), is useful in this regard. We calculated lambda1 from 2 channel ictal EEG data recorded in 25 depressed subjects who received right unilateral ECT. We studied the relationship of lambda1 to treatment therapeutic outcome and to an indirect measure of treatment therapeutic potency, the extent to which the stimulus intensity exceeds the seizure threshold. We found lambda1 could be reliably calculated from ictal EEG data and that the global mean, maximum, and standard deviation of lambda1 were smaller in the more therapeutically potent moderately suprathreshold ECT and in therapeutic responders. These results imply a more predictable or consistent pattern of EEG seizure activity over time in more therapeutically effective ECT seizures. These findings also suggest the promise of lambda1 as a marker of ECT seizure therapeutic adequacy and build on our previous work suggesting that lambda1 may be useful for classifying seizures and for reflecting the relative physiologic impact of seizure activity.

Adult↗
PubMed1997

Lack of relapse with tryptophan depletion following successful treatment with ECT.

OBJECTIVE: Although the antidepressant mechanism of ECT is unknown, there are considerable data to support serotonergic involvement. The effects of tryptophan depletion were studied in patients with major depression treated successfully with ECT. METHOD: Five patients who had been successfully treated with ECT for major depression were studied in a randomized, double-blind, crossover design comparing tryptophan depletion to a placebo procedure. RESULTS: No effect of tryptophan depletion on mood symptoms was observed despite more than an 85% decrease in total serum tryptophan. CONCLUSIONS: These data suggest that presynaptic serotonin availability may not be necessary for the acute maintenance of an antidepressant response to ECT.

Adult↗
PubMed1996

Effect of ECT treatment number on the ictal EEG.

Recent evidence suggests that attributes of the ictal electroencephalogram (EEG) may be clinically useful for estimating the extent to which the electroconvulsive therapy (ECT) stimulus exceeds the seizure threshold (relative stimulus intensity). Such a tool could allow a practitioner, who chose, on the basis of expected therapeutic response and side effect rates, to implement stimulus dosing to maintain relative stimulus intensity over the treatment course, despite the uncertain rise in seizure threshold that occurs. One potential confounding factor is a possible systematic change in the ictal EEG over the treatment course that is not due to changes in seizure threshold. We explored the effect of treatment number by comparing ictal EEG data obtained at treatments across the ECT course that were delivered at the identical relative stimulus intensity. We found that the ictal EEG at treatment 1 was characterized by a greater mid-ictal amplitude and post-ictal suppression (trend) than subsequent treatments for barely suprathreshold unilateral ECT, but not for barely suprathreshold bilateral or moderately suprathreshold unilateral ECT, and that this change may affect therapeutic effectiveness. These findings suggest the importance of treatment-number effects for the clinical application of the ictal EEG and point to possible physiological differences between unilateral and bilateral ECT.

Adult↗
PubMed1996

A comparison of EEG signal dynamics in waking, after anesthesia induction and during electroconvulsive therapy seizures.

Evidence suggests that quantitative dynamical measures of electroencephalogram (EEG) signals are more appropriate for characterizing the differences between states in an individual rather than as absolute indices. One such measure, the largest Lyapunov exponent (lambda 1), appears to have potential for identifying seizure activity and for being of clinical utility for characterizing electroconvulsive therapy (ECT) seizures. As a result, we compared lambda 1 for the EEG recorded in 8 depressed subjects in 3 states: (1) during right unilateral ECT seizures, (2) during the pre-ECT waking state, and (3) following anesthesia administration but prior to ECT. Spectral amplitude and autocorrelation were also calculated in these states, allowing a comparison of these measures with lambda 1. We hypothesized that lambda 1 would be lowest during the ECT seizures, suggestive of greater EEG signal predictability over time during the seizures. We found that during the seizures lambda 1 was smaller, while spectral amplitude was larger. Significant inter-state differences were not found for the left temporal and occipital regions suggesting that these measures might serve as markers of the degree of seizure involvement of specific brain regions. Spectral amplitude and lambda 1 were uncorrelated and varied independently in some cases. The autocorrelation time was shortest in the waking EEG, and longest for the post-anesthesia EEG, and did not account for the differences seen in lambda 1. In contrast, the persistence of oscillations in the autocorrelation functions was greater for the ictal EEG than the other two states and may relate to lambda 1.

Adult↗
PubMed1996

Serum prolactin, electrode placement, and the convulsive threshold during ECT.

This study examines the relationship of serum prolactin changes (delta PRL) to variations in electrode placement after controlling for differences in the convulsive threshold. Previous studies showing greater release of PRL with bilateral (BL) compared with right unilateral (RUL) electrode placement were conducted without knowledge of the convulsive threshold. Twenty-two patients each received threshold RUL, threshold BL, 2.25 times threshold RUL, and 2.25 times threshold BL ECT. Serum PRL was collected 5 min before and 15 min after each electroconvulsive therapy (ECT). The convulsive threshold was greater for BL than RUL electrode placement. delta PRL was greater with BL than RUL ECT at comparable relative stimulus intensities. delta PRL was not correlated with seizure duration or absolute stimulus dose.

Electroconvulsive Therapy↗
PubMed1996

The relative ability of three ictal EEG frequency bands to differentiate ECT seizures on the basis of electrode placement, stimulus intensity, and therapeutic response.

Ictal EEG indices show promise for separating individual ECT seizures on the basis of treatment electrode placement (ELPL), relative stimulus intensity (Dose), and expected therapeutic response. One factor impeding the effective clinical implementation of ictal EEG indices for these purposes is uncertainty as to the relative utility of lower and higher frequency EEG activity. Recent articles are contradictory in this regard, but no data exist addressing this issue. As a result, we reanalyzed data from 44 subjects in two studies and compared the relative ability of ictal EEG data in three frequency bands to differentiate seizures as a function of ELPL, Dose, and therapeutic response. We found that the frequency band that best differentiated these groups depended on the EEG measure used, the temporal portion of the seizure, and whether ELPL, Dose, or therapeutic response was being compared.

Algorithms↗
PubMed1995

Seizure threshold in electroconvulsive therapy (ECT) II. The anticonvulsant effect of ECT.

To measure the anticonvulsant effects of a course of electroconvulsive therapy (ECT), we used a flexible stimulus dosage titration procedure to estimate seizure threshold at the first and sixth ECT treatments in 62 patients with depression who were undergoing a course of brief pulse, constant current ECT given at moderately suprathreshold stimulus intensity. Seizure threshold increased by approximately 47% on average, but only 35 (56%) of the 62 patients showed a rise in seizure threshold. The rise in seizure threshold was associated with increasing age, but not with gender, stimulus electrode placement, or initial seizure threshold. Dynamic impedance decreased by approximately 5% from the first to the sixth ECT treatment, but there was no correlation between the change in dynamic impedance and the rise in seizure threshold. No relation was found between the rise in seizure threshold and either therapeutic response status or speed of response to the ECT treatment course. These findings confirm the anticonvulsant effect of ECT but suggest that such effects are not tightly coupled to the therapeutic efficacy of moderately suprathreshold ECT.

Adult↗
PubMed1995

Seizure threshold in electroconvulsive therapy: I. Initial seizure threshold.

We measured initial seizure threshold by means of a structured stimulus dosage titration procedure in a clinical sample of 111 depressed patients undergoing brief-pulse, constant-current electroconvulsive therapy (ECT). Initial seizure threshold was approximately 60 millicoumbs (mc) (10 Joules) on average, but varied widely (6-fold) across patients. Initial seizure threshold was predicted by four variables: electrode placement (higher with bilateral), gender (higher in men), age (higher with increasing age), and dynamic impedance (inverse relationship). Use of neuroleptic medication was associated with a lower seizure threshold. EEG seizure duration was inversely related to initial seizure threshold, but no other relations with seizure duration were found. These findings may have important clinical implications for stimulus dosing strategies in ECT.

Adult↗
PubMed1995

The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT.

Relative stimulus intensity above seizure threshold has been shown to affect therapeutic outcome with unilateral ECT. The authors sought to explore whether a multivariate ictal EEG model would permit ongoing clinical assessment of this parameter. Twenty-five depressed subjects were randomized to either barely (T) or moderately (2.5T) suprathreshold ECT treatments. Seizures in 2.5T subjects had significantly greater ictal spectral amplitude and coherence, greater postictal suppression, and shorter latency until ictal slow-wave onset. A multivariate logistic regression ictal EEG model distinguished between stimulus intensity groups with 90% accuracy. Preliminary evidence suggests a relationship between several ictal EEG indices and therapeutic outcome. A multivariate ictal EEG algorithm holds promise as a tool for clinical determination of adequate stimulus intensity with unilateral ECT.

Adult↗
PubMed1995

ECT seizure duration: reliability of manual and computer-automated determinations.

Reliable monitoring of electroencephalographic (EEG) and electromyographic electroconvulsive therapy (ECT) seizure duration has become important as these assessments have become a routine part of the clinical practice of ECT. In this regard, accurate automated seizure duration determinations would be particularly valuable. As a result, the present study was performed to assess the reliability of available computer-automated determinations of seizure duration (Thymatron Model DGx ECT machine; Somatics, Inc.) and to explore the factors upon which such reliability as well as the determinations of experienced raters depend. We found that the experienced human raters had very high interrater reliability, significantly higher than either did with the automated Thymatron DGx ratings. In general, the reliability of all ratings declined in the context of artifact, poor postictal suppression, or an EEG seizure end point that was reached gradually. Reliability was also greater for continuation ECT as compared with the index course. The reliability of Thymatron DGx versus experienced human ratings was particularly sensitive to these factors, ranging from 0.68 when several of these factors were simultaneously present to 0.999 when all these factors were absent.

Adult↗
PubMed1994

The present use of electroconvulsive therapy.

Physicians attempting to treat certain severe mental disorders have recently shown renewed interest in electroconvulsive therapy (ECT). A number of technical innovations have made ECT safer, as well as more effective. These innovations include oxygenation, muscular relaxation, unilateral nondominant electrode placement, use of brief-pulse stimuli, titrated stimulus dosing, electroencephalographic (EEG) monitoring, determination of seizure adequacy, and pharmacologic enhancement of treatment response.

Electroconvulsive Therapy↗