Forms Of Electroconvulsive Therapy Research Articles

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT)

BackgroundFocal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. MethodsUsing a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD24). ResultsIn the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD24 score over time (F1,35 = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. ConclusionsFEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

An Open-Label, Pilot Study of Daily Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy

Right unilateral ultrabrief (RUL-UB) pulse width electroconvulsive therapy (ECT) has attracted much research attention recently due to its smaller effect on memory than is associated with other forms of ECT, such as bitemporal placement or unilateral standard pulse width. However, RUL-UB has demonstrated slower antidepressant efficacy in comparison to the other techniques. One method to enhance the speed of response to RUL-UB ECT is administration of 5 times a week (termed "daily") treatments as opposed to the more standard twice or thrice weekly schedule. In this open label study, we treated 20 depressed patients with daily RUL-UB treatments for up to 2 weeks (ie, 10 treatments) using standardized assessments of depression and retrograde amnesia. Response and remission rates were commensurate with those reported in other recent studies using this technique with twice or thrice weekly treatment frequencies, and there was no clinically significant effect on retrograde memory function. We conclude that daily administration of RUL-UB ECT may shorten the duration of the course of ECT treatments without compromising cognition. A randomized trial comparing this technique to a thrice weekly schedule of RUL-UB treatments is indicated.

Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: influence of white matter anisotropic conductivity.

We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.

The effect of electrode placement and pulsewidth on asystole and bradycardia during the electroconvulsive therapy stimulus

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, and different forms are increasingly used in clinical practice. This study investigated the acute cardiac effects of different forms of ECT: bitemporal and bifrontal (1.5 times seizure threshold), and right unilateral (RUL) (five times seizure threshold). For RUL ECT, the effect of stimulus pulsewidth (1.0 or 0.3 ms) was also examined. Electrocardiograms recorded just prior to and during the ECT stimulus in 476 ECT treatments in 114 patients were examined. The degree of bradycardia (any slowing of heart rate) and incidence of asystole (absence of heart beats for ≥5 s) during the ECT stimulus were measured from these traces. Regression analyses estimated the contribution of patient and ECT treatment factors to the risk of bradycardia and asystole. Bifrontal ECT was associated with less severe bradycardia than bitemporal or RUL ECT (p<0.001). Modelling showed, for a mean pre-ECT heart rate of 85 beats per minute (bpm), expected heart rates during the stimulus were 78 bpm (bifrontal), 46 bpm (bitemporal) and 35 bpm (RUL). Bifrontal ECT was also associated with a lower incidence of asystole than RUL ECT (corrected odds ratio 1:207) and bitemporal ECT (corrected odds ratio 1:24). Ultrabrief pulsewidth stimulation resulted in lesser bradycardia and asystole than standard pulsewidth stimulation for RUL ECT. Modelling showed, for a mean pre-ECT heart rate of 86 bpm, expected heart rates were 43 bpm (ultrabrief RUL) and 26 bpm (RUL). Bradycardia and asystole were relatively common side-effects during the ECT stimulus. Bifrontal ECT was associated with the lowest risk of bradycardia and asystole during ECT and should be considered for patients at risk of arrhythmias and prolonged asystole during ECT.

Prediction of antidepressant response in both 2.25 × threshold RUL and fixed high dose RUL ECT

Some forms of electroconvulsive therapy (ECT) can result in generalized seizures that lack efficacy, therefore physiological markers of treatment adequacy would be helpful. EEG measures of seizure quality, such as EEG regularity and post-ictal suppression, have largely supplanted seizure duration as a marker for seizure adequacy, yet no predictive algorithm has gained wide clinical acceptance. Electrographic seizure durations of less than 25 s still prompt re-stimulation in many settings. We re-examined the utility of EEG seizure duration and other measures of EEG seizure as predictors of antidepressant response to right unilateral (RUL) ECT. MethodsSeventy-two adult patients with major depression were randomized to either titrated RUL ECT at 2.25 times initial seizure threshold or RUL ECT at a fixed dose of 403 mC. Intent-to-treat responder status (defined by 60% reduction in HRSD scores and final score of 12 or less after the last RUL ECT session) was identified as the dependent variable in a nominal logistic regression model including EEG seizure quality candidate variables, controlled for age and gender. ResultsA model including EEG seizure duration, EEG regularity, post-ictal suppression, age and gender and randomization status was significantly predictive of intent-to-treat responder status at treatment 2 (R2=.21 p<.003; N=66) and treatment 4 (R2=.27 p<.0004; N=67). The model remained significant at these time points even when randomization status (titrated moderately suprathreshold vs. high fixed dosage) was removed (Treatment 2: R2=.18 p<.007; Treatment 4: R2=.23 p<.0007). ConclusionEEG markers of seizure adequacy, including EEG seizure duration, are modestly predictive of antidepressant response for both titrated moderately suprathreshold and high fixed dosage RUL ECT.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT

Background Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Methods Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Results Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Limitations Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. Conclusions This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis

To investigate if repetitive transcranial magnetic stimulation (rTMS) was as effective as electroconvulsive therapy (ECT) in treating major depressive episodes and to perform a cost-effectiveness analysis. A single-blind pragmatic multicentre randomised controlled trial (RCT) with 6 months of follow-up to test equivalence of rTMS with ECT. The South London and Maudsley NHS Trust and Pembury Hospital in the Invicta Mental Health Trust in Kent. Right-handed adult patients referred for ECT for treatment of a major depressive episode (DSM-IV) were assessed. During the 2.5-year trial period, 260 patients were referred for ECT, of whom 46 entered the trial. The main reason for not entering the trial was not consenting to ECT while being formally treated under the UK Mental Health Act 1983. Patients were randomised to receive a 15-day course of rTMS of the left dorsolateral prefrontal cortex (n = 24) or a course of ECT (n = 22). Patients were assessed before randomisation, at end of treatment and at the 6-month follow-up. Primary outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD) and proportion of remitters (defined as HRSD score <or=8) at the end-of-treatment time point. Secondary outcomes included self-ratings for mood on the Beck Depression Inventory-II (BDI-II) and visual analogue mood scales (VAMS), the Brief Psychiatric Rating Scale (BPRS), plus subjective and objective side-effects. Low scores on the BDI-II, VAMS and BPRS are positive in terms of health. The results were analysed on an intention-to-treat basis. Cost data were collected using the Client Service Receipt Inventory and the Short Form with 36 Items was used to obtain quality of life measures. Health economic outcomes were cost of treatments, costs incurred during the 6-month follow-up period and gains in quality-adjusted life-years (QALYs). One patient was lost to follow-up at end of treatment and another eight at 6 months. The end-of-treatment HRSD scores were lower for ECT, with 13 (59%) achieving remission compared with four (17%) in the rTMS group. However, HRSD scores did not differ between groups at 6 months. BDI-II, VAMS and BPRS scores were lower for ECT at end of treatment and remained lower after 6 months. Improvement in subjective reports of side-effects following ECT correlated with antidepressant response. There was no difference between the two groups before or after treatment on global measures of cognition. Although individual treatment session costs were lower for rTMS than ECT, the cost for a course of rTMS was not significantly different from that for a course of ECT as more rTMS sessions were given per course. Service costs were not different between the groups in the subsequent 6 months but informal care costs were significantly higher for the rTMS group and contributed substantially to the total cost for this group during the 6-month follow-up period. There also was no difference in gain in QALYs for ECT and rTMS patients. Analysis of cost-effectiveness acceptability curves demonstrated that rTMS has very low probability of being more cost-effective than ECT. ECT is a more effective and potentially cost-effective antidepressant treatment than 3 weeks of rTMS as administered in this study. Optimal treatment parameters for rTMS need to be established for treating depression. More research is required to refine further the administration of ECT in order to reduce associated cognitive side-effects while maintaining its effectiveness. There is a need for large-scale, adequately powered RCTs comparing different forms of ECT. The next generation of randomised trials of rTMS should also seek to compare treatment variables such as stimulus intensity, number of stimuli administered and duration of treatment, with a view to quantifying an effect size for antidepressant action.

Evaluation and Comparison of EEG Traces: Latent Structure in Nonstationary Time Series

We explore and illustrate the use of time series decomposition methods for evaluating and comparing latent structure in nonstationary electroencephalographic (EEG) traces obtained from depressed patients during brain seizures induced as part of electroconvulsive therapy (ECT). Analysis of the patterns of change over time in the frequency structure of such EEG data provides insight into the neurophysiological mechanisms of action of this effective but poorly understood antidepressant treatment, and allows clinicians to modify ECT treatments to optimize therapeutic benefits while minimizing associated side effects. Our work has introduced new methods of time-frequency analysis of EEG series that identify the complete pattern of time evolution of frequency structure over the course of a seizure, and usefully assist in these scientific and clinical studies. New methods of decomposition of flexible dynamic models provide time domain decompositions of individual EEG series into collections of latent components in different frequency bands. This allows us to explore ECT seizure characteristics via inferences on the time-varying parameters that characterize these latent components, and to relate differences in such characteristics across seizures to differences in the therapeutic effectiveness and cognitive side effects of those seizures. This article discusses the scientific context and problems, development of nonstationary time series models and new methods of decomposition to explore time-frequency structure, and aspects of model fitting and analysis. We include applied studies on two datasets from recent clinical ECT studies. One is an initial illustrative analysis of a single EEG trace, the second compares the EEG data recorded during two types of ECT treatment that differ in therapeutic effectiveness and cognitive side effects. The uses of these models and time series decomposition methods in extracting and contrasting key features of the seizure underlying the EEG signals are highlighted. Through the use of these models we have quantified, for the first time, decreases in the dominant frequencies of low-frequency EEG components during ECT seizures. We have also identified preliminary evidence that such decreases are enhanced under the more effective ECTs at higher electrical dosages, a finding consistent with prior reports and the hypothesis that more effective forms of ECT are more effective in eliciting neurophysiological inhibitory processes.

Evaluation and Comparison of EEG Traces: Latent Structure in Nonstationary Time Series

We explore and illustrate the use of time series decomposition methods for evaluating and comparing latent structure in nonstationary electroencephalographic (EEG) traces obtained from depressed patients during brain seizures induced as part of electroconvulsive therapy (ECT). Analysis of the patterns of change over time in the frequency structure of such EEG data provides insight into the neurophysiological mechanisms of action of this effective but poorly understood antidepressant treatment, and allows clinicians to modify ECT treatments to optimize therapeutic benefits while minimizing associated side effects. Our work has introduced new methods of time-frequency analysis of EEG series that identify the complete pattern of time evolution of frequency structure over the course of a seizure, and usefully assist in these scientific and clinical studies. New methods of decomposition of flexible dynamic models provide time domain decompositions of individual EEG series into collections of latent components in different frequency bands. This allows us to explore ECT seizure characteristics via inferences on the time-varying parameters that characterize these latent components, and to relate differences in such characteristics across seizures to differences in the therapeutic effectiveness and cognitive side effects of those seizures. This article discusses the scientific context and problems, development of nonstationary time series models and new methods of decomposition to explore time-frequency structure, and aspects of model fitting and analysis. We include applied studies on two datasets from recent clinical ECT studies. One is an initial illustrative analysis of a single EEG trace, the second compares the EEG data recorded during two types of ECT treatment that differ in therapeutic effectiveness and cognitive side effects. The uses of these models and time series decomposition methods in extracting and contrasting key features of the seizure underlying the EEG signals are highlighted. Through the use of these models we have quantified, for the first time, decreases in the dominant frequencies of low-frequency EEG components during ECT seizures. We have also identified preliminary evidence that such decreases are enhanced under the more effective ECTs at higher electrical dosages, a finding consistent with prior reports and the hypothesis that more effective forms of ECT are more effective in eliciting neurophysiological inhibitory processes.

EEG manifestations during ECT: effects of electrode placement and stimulus intensity

This study examined the ictal electroencephalographic (EEG) characteristics of four forms of electroconvulsive therapy (ECT) known to differ in efficacy. Previously, we demonstrated that titrated, low-dose right unilateral ECT reliably produces generalized seizure of adequate duration, but is remarkably weak in antidepressant effects. Using a new rating scale, we found that specific features of the ictal and immediate postictal EEG varied significantly with ECT stimulus intensity and electrode placement. The low-dose right unilateral condition differed from more effective forms of ECT in having the longest polyspike phase duration, averaging twice that of the other conditions; it was also the condition least likely to manifest bioelectric suppression immediately following seizure termination. In contrast, high-dose bilateral ECT—a treatment with particularly rapid antidepressant effects—resulted in the greatest peak slow-wave amplitude in both hemispheres. Total seizure duration did not differ among the four treatment conditions. These findings indicate that seizure duration is not a useful marker of therapeutic efficacy, and instead provide preliminary evidence that other features of the EEG may be more useful markers of treatment adequacy.

Monitoring the duration of electroconvulsive therapy seizures: 'cuff' and EEG methods compared.

Seizure durations in electroconvulsive therapy (ECT) were determined by both EEG and BP cuff methods in 20 patients receiving 225 seizures. The estimates were highly correlated, with cuff estimates 10% shorter than those by EEG. Routine monitoring of seizure duration by the BP cuff method is recommended, particularly in unilateral ECT. Monitoring seizure time should resolve controversies over the efficacy of different forms of ECT, as well as improve clinical practice where disturbing reports of missed seizures are now documented.