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Biomedical subjects

A D Krystal

Publications and source records attributed to A D Krystal.

At least 19 recordsLinked to original sources
PubMed2001

The use of valerian in neuropsychiatry.

Valerian is a medicinal agent deriving from the plant Valeriana officinalis L. We reviewed the available literature on the use of valerian preparations in the treatment of neuropsychiatric disorders. Preclinical studies suggest that valerian has sedative and muscle-relaxant effects. Few clinical trials with valerian have been carried out in conditions other than insomnia. The insomnia studies have methodologic shortcomings but suggest that some preparations lead to significant subjective improvement in sleep complaints with remarkably few side effects. Furthermore, some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. If this safety profile and the plant's sedative/hypnotic efficacy are confirmed in double-blind, placebo-controlled trials with carefully and consistently prepared valerian compounds, then those compounds would fill an important and presently unfilled niche in the treatment of insomnia.

Journal Article↗
PubMed2000

EEG effects of ECT: implications for rTMS.

Electroconvulsive therapy (ECT) involves the use of electrical stimulation to elicit a series of generalized tonic-clonic seizures for therapeutic purposes and is the most effective treatment known for major depression. These treatments have significant neurophysiologic effects, many of which are manifest in the electroencephalogram (EEG). The relationship between EEG data and the response to ECT has been studied since the 1940s, but for many years no consistent correlates were found. Recent studies indicate that a number of specific EEG features recorded during the induced seizures (ictal EEG) as well as before and after a course of treatment (interictal EEG) are related to both the therapeutic efficacy and cognitive side effects. Similar to ECT, repetitive transcranial magnetic stimulation (rTMS), which involves focal electromagnetic stimulation of cortical neurons, has also been studied as an antidepressant therapy and also appears to have neurophysiologic effects, although these have not been as fully investigated as is the case with ECT. Given the similarity of these treatments, it is natural to consider whether advances in understanding the electrophysiologic correlates of the ECT response might have implications for rTMS. The present article reviews the literature on the EEG effects of ECT and discusses the implications in terms of the likely efficacy and side effects associated with rTMS in specific anatomic locations, the potential for producing an antidepressant response with rTMS without eliciting seizure activity, eliciting focal seizures with rTMS, and the possibility of using rTMS to focally modulate seizure induction and spread with ECT to optimize treatment.

Brain Mapping↗
PubMed2000

Prediction of the utility of a switch from unilateral to bilateral ECT in the elderly using treatment 2 ictal EEG indices.

BACKGROUND: The choice of whether to administer nondominant unilateral (UL) or bilateral (BL) ECT remains controversial. METHODS: A study in which moderately suprathreshold UL nonresponders at treatment 6 were randomized to UL or BL ECT offered the opportunity to explore whether ictal EEG indices at treatment 2 might predict response to UL ECT, and also which UL ECT nonresponders are likely to respond to BL ECT. RESULTS: We found that less postictal suppression in response to the second UL ECT stimulus was predictive of a poorer subsequent therapeutic response to UL ECT, but of a better therapeutic response if switched to BL ECT. A multivariate ictal EEG model was developed that had a significant capacity to differentiate those who will respond to UL ECT versus those who will not respond to UL ECT, but who will be therapeutic responders when switched to BL ECT. CONCLUSIONS: This study raises the possibility that ictal EEG indices at treatment 2 may identify situations when UL ECT is physiologically and therapeutically inadequate, and when BL ECT is likely to be more effective. The determination of whether such predictive physiologic models are of clinical utility for the prediction of outcome awaits further study.

Aged↗
PubMed2000

The development and retrospective testing of an electroencephalographic seizure quality-based stimulus dosing paradigm with ECT.

The optimization of electroconvulsive therapy (ECT) stimulus dosing remains uncertain. Previous work suggests the potential utility of ictal EEG models of seizure adequacy, but such models have never been tested for their ability to improve the clinical dosing of ECT treatments. Using data from 149 depressed patients, the authors developed an ictal electroencephalographic (EEG) model that can discriminate seizures produced by more therapeutically effective and less efficacious types of stimuli. They retrospectively determined how stimulus dosing according to this seizure adequacy-based model would have differed from that actually used in an additional 61 patients who received ECT according to a standard clinical dose-titration and EEG seizure duration-based dosing strategy. Although the model indicated an increase in stimulus intensity at some point during the ECT treatment course in 23 of 61 patients, only 5 of these 23 actually received a clinical increase in stimulus intensity. The patients who did not receive this increase had a significantly diminished therapeutic response compared with the other patients. Conversely, the model also indicated that an increase in stimulus intensity that occurred clinically might have been unnecessary to achieve therapeutic efficacy in 11% of the patients. This study provides preliminary evidence that ictal EEG models have the potential to make clinically relevant seizure adequacy distinctions among ECT treatments. Further prospective work is indicated to determine the clinical utility of such models.

Adult↗
PubMed2000

ECT stimulus intensity: are present ECT devices too limited?

OBJECTIVE: The maximum output charge for ECT devices is limited to 576 millicoulombs in the United States, although there are no data ensuring that this limit will allow consistently effective treatments. The authors examined whether this limit has a negative impact on therapeutic response and, therefore, whether a higher stimulus charge should be available. METHOD: They retrospectively reviewed the records of 471 patients who received a clinical index course of ECT at Duke University between 1991 and 1998. These patients received conservative stimulus dosing of 2.25 times seizure threshold for unilateral ECT and 1.5 times seizure threshold for bilateral ECT. RESULTS: Seventy-two (15%) of the 471 patients required the maximum stimulus intensity during their index ECT course. Of these, 24 (5% of the total) had either a short EEG seizure (less than 25 seconds) or had no seizure at the maximum level. Strategies to augment therapeutic response with caffeine, ketamine, or hyperventilation were used in 14 of the 24 patients, and data on therapeutic response were available for 22 of the 24. Only seven (32%) of these 22 patients were considered ECT responders, compared with 242 (66%) of the remaining 364 patients for whom data on response to ECT were available. Older age and pre-ECT course EEG slowing were predictors of requiring the maximum stimulus level. CONCLUSIONS: The maximum available stimulus output was therapeutically insufficient for 5% of the patients studied even when available means to augment response were instituted. This percentage would likely be even larger with the use of a less conservative dosing protocol for unilateral ECT. Increases in maximum stimulus output for ECT devices should be considered as a means to ensure adequate treatment response.

Brain↗
PubMed1999

New methods of time series analysis of non-stationary EEG data: eigenstructure decompositions of time varying autoregressions.

OBJECTIVE: Those who analyze EEG data require quantitative techniques that can be validly applied to time series exhibiting ranges of non-stationary behavior. Our objective is to introduce a new analysis technique based on formal non-stationary time series models. This novel method provides a decomposition of the time series into a set of 'latent' components with time-varying frequency content. The identification of these components can lead to practical insights and quantitative comparisons of changes in frequency structure over time in EEG time series. METHODS: The technique begins with the development of time-varying autoregressive models of the EEG time series. Such models have been previously used in EEG analysis but we extend their utility by the introduction of eigenstructure decomposition methods. We review the basis and implementation of this method and report on the analysis of two channel EEG data recorded during 3 generalized tonic-clonic seizures induced in an individual as part of a course of electroconvulsive therapy for major depression. RESULTS: This technique identified EEG patterns consistent with prior reports. In addition, it quantified a decrease in dominant frequency content over the seizures and suggested for the first time that this decrease is continuous across the end of the seizures. The analysis also suggested that the seizure EEG may be best modeled by the combination of multiple processes, whereas post-ictally there appears to be one dominant process. There was also preliminary evidence that these features may differ as a function of ECT therapeutic effectiveness. CONCLUSIONS: Eigenanalysis of time-varying autoregressive models has promise for improving the analysis of EEG time series.

Brain↗
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

Sleep in peri-menopausal and post-menopausal women.

Despite the fact that a large number of women report sleep disturbances associated with peri-menopausal and post-menopausal periods, there is a surprising lack of literature related to this issue. In fact, there has not been enough work in this area to even definitively establish whether there is a sleep disorder that is specifically related to these life-stage changes. Herein we review the available literature which suggests that insomnia may be directly linked to the changes that occur during the peri/post-menopausal periods. This insomnia appears to be due to night sweats caused by the hormonal changes which occur and which lead to an increase in arousals. Persistence of insomnia symptoms after adequate hormone replacement therapy may indicate that behavioral conditioning of the insomnia initially triggered by the night sweats may have occurred. Alternatively, such an insomnia in a peri/post-menopausal woman could be due to unresolved grief related to going through menopause or could reflect an independent sleep disorder, such as periodic movements of sleep, sleep apnea, depression, anxiety, etc. Whereas menopausal changes do not directly lead to an increase in sleep apnea they seemingly contribute to an increased risk for this disorder. In view of these considerations, we provide guidelines for the proper diagnosis and treatment of peri/post-menopausal women with sleep complaints.

Journal Article↗
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

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

Neuropsychiatric considerations in the use of electroconvulsive therapy.

ECT is an effective and rapidly acting treatment for certain major psychiatric disorders, even in patients with neurologic illness. Further, in some cases the neurologic illness itself also responds to ECT. Patients with some types of neurologic illness may be at increased risk of neurologic or cognitive side effects from ECT, but these risks can be lowered by careful pre-ECT evaluation and optimal ECT technique.

Brain Diseases↗
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

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↗
PubMed1996

The empirical identification of insomnia subtypes: a cluster analytic approach.

Over the past 15 years, there has been considerable debate concerning the extent to which insomnia patients can be classified into diagnostic subtypes. Despite this debate, relatively little research has been conducted to empirically determine whether naturally occurring insomnia subtypes might be identified within populations of sleep clinic patients. In the current study we used a hierarchical cluster analysis to empirically identify subtypes among a mixed group of normal sleepers and the insomnia outpatients who presented to our sleep center over the past decade. Using factor-analytically derived composite variables that summarized data obtained from sleep history questionnaires and polysomnographic monitoring, this clustering procedure resulted in the identification of 14 subgroups that varied between four and 34 patients/subjects in size. Subsequently, subgroup mean scores for the composite variables used in the clustering procedure were used to construct profiles for each of the 14 clusters. A multivariate profile analysis, employed to elucidate subgroup differences, showed that these cluster profiles differed in terms of their configural shapes, average elevations, and degrees of interscale differences. Furthermore, both DSM-III-R (American Psychiatric Association) and International Classification of Sleep Disorders (ICSD) insomnia diagnoses, assigned independent of cluster findings, suggested that these subtypes differed significantly in regard to their diagnostic compositions. Nevertheless, a far-from-perfect concordance was observed between such clinically assigned diagnoses and cluster group membership. In fact, many of the empirically identified groups were composed of various DSM-III-R and/or ICSD diagnostic subtypes. These results provided only partial support for current DSM and ICSD insomnia categories. However, our results support the existence of multiple, clinically discrete insomnia subtypes and provide information that may be useful in future revisions of current insomnia nosologies.

Adult↗