Richard D. Weiner

Effects of Stimulus Parameters on Cognitive Side Effects

This symposium has already focused on recent experimental data directed toward an understanding of the differential effects of electrode placement upon both therapeutic response and adverse cognitive effects with electrmnvulsive therapy (ECT). In addition, we have yet to hear a number of further expositions on this subject. The available data, presented both here and elsewhere, suggest that unilateral nondominant (UL) ECT is roughly as effective as bilateral (BL) ECT in producing a remission in severely depressed patients.’” At the same time, it must be pointed out that technical factors such as sufficient interelectrode distance and the assurance of suprathreshold stimuli also appear to play a role in the efficacy of UL treatments. In addition, there is also a possibility that some patients might respond better to the combination of more intense seizures and denser organic interictal changes produced by bilateral stimulation. The situation with regard to adverse effects, however, is considerably clearer: unilateral nondominant ECT offers a distinct advantage to bilateral treatments with regard to the presence and extent of cognitive disruption, a t least with respect to those functions that depend on the dominant herni~phere.~ Still, the extent of data indicating that such amnestic differences exist longer than a few weeks has been largely limited to reports of self-ratings.Another form of ECT modification, discussed both within this volume as well as elsewhere in the literature, though to a lesser degree than electrode placement, is the

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.

Does electroconvulsive therapy cause brain damage

Although the use of ECT has declined dramatically from its inception, this decrease has recently shown signs of leveling out because of ECTs powerful therapeutic effect in severely ill depressed individuals who either do not respond to pharmacologic alternatives or are too ill to tolerate a relatively lengthy drug trial. Notwithstanding its therapeutic benefits, ECT has also remained a controversial treatment modality, particularly in the eye of the public. Given the unsavory qualities associated with the word “electroconvulsive,” claims of possible, probable, or even certain brain damage with ECT have easily found listeners. A careful, nonselective assessment of data covering the areas of pathology, radiology, electrophysiology, biochemistry, and neuropsychology leads both to certain conclusions and to certain unanswered questions. ECT is not the devastating purveyor of wholesale brain damage that some of its detractors claim. For the typical individual receiving ECT, no detectable correlates of irreversible brain damage appear to occur. Still, there remains the possibility that either subtle, objectively undetectable persistent deficits, particularly in the area of autobiographic memory function, occur, or that a rarely occurring syndrome of more pervasive persistent deficits related to ECT use may be present. Clearly, more research directed toward answering these questions needs to be carried out so that the role of ECT can be more rigorously defined. While such research is pending, however, we cannot expect that the conditions that predispose to clinical referrals for ECT will disappear. Given the misery, anguish, and risk of death by suicide, starvation, or debilitation associated with severe depressive illness, for example, it still appears that ECT, at least for the present, must continue to be available.

Association of trauma exposure with psychiatric morbidity in military veterans who have served since September 11, 2001

OBJECTIVE This study examined the association of lifetime traumatic stress with psychiatric diagnostic status and symptom severity in veterans serving in the US military after 9/11/01. METHOD Data from 356 US military veterans were analyzed. Measures included a standardized clinical interview measure of psychiatric disorders, and paper-and-pencil assessments of trauma history, demographic variables, intellectual functioning, posttraumatic stress disorder (PTSD) symptoms, depression, alcohol misuse, and global distress. RESULTS Ninety-four percent of respondents reported at least one traumatic stressor meeting DSM-IV criterion A for PTSD (i.e., life threatening event to which the person responded with fear, helplessness or horror), with a mean of four criterion A traumas. Seventy-one percent reported serving in a war-zone, with 50% reporting occurrence of an event meeting criterion A. The rate of current psychiatric disorder in this sample was: 30% PTSD, 20% major depressive disorder, 6% substance abuse or dependence and 10% for the presence of other Axis I psychiatric disorders. After accounting for demographic covariates and combat exposure, childhood physical assault and accident/disasters were most consistently associated with increased likelihood of PTSD. However, PTSD with no comorbid major depressive disorder or substance use disorder was predicted only by combat exposure and adult physical assault. Medical/unexpected-death trauma and adult physical assault were most consistently associated with more severe symptomatology. CONCLUSIONS Particular categories of trauma were differentially associated with the risk of psychiatric diagnosis and current symptom severity. These findings underscore the importance of conducting thorough assessment of multiple trauma exposures when evaluating recently post-deployed veterans.

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.

The effects of ECT stimulus dose and electrode placement on the Ictal electroencephalogram: An intraindividual crossover study

Recent evidence suggests that electroconvulsive therapy (ECT) efficacy depends upon both electrode placement and the degree to which stimulus dosage exceeds seizure threshold (T), and not simply on surpassing a minimum seizure duration as has been assumed. In light of these findings and studies reporting ictal electroencephalogram (EEG) differences between bilateral and unilateral ECT, we performed this 19-subject intraindividual crossover study of the effects of dose and electrode placement on the ictal EEG. We found ictal EEG evidence of greater seizure intensity with bilateral than unilateral ECT and with higher dosage (2.25 T) compared with barely suprathreshold stimuli. Seizure duration was not longer with bilateral than unilateral ECT and actually decreased with increased dose. A number of ictal EEG variables separated the unilateral 2.25 T and unilateral T conditions, which reportedly differ in efficacy, and therefore, these EEG measures show promise as markers of treatment adequacy.

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.

Severity of subcortical gray matter hyperintensity predicts ECT response in geriatric depression

Objective To determine the effect of subcortical white and gray matter lesions on ECT outcome. Method 41 geriatric psychiatric inpatients underwent an MRI scan during their ECT work-up. Periventricular, deep white matter, and subcortical gray matter hyperintensities were graded. The associations of low versus high hyperintensity ratings and symptom scores, Clinical Global Impression severity (CGS) ratings, Montgomery-Asberg Depression Scale score, and number of treatments were examined using t-tests and repeated measures ANOVA. Results Patients with more severe subcortical gray hyperintensities (SCG) had significantly less improvement as measured by CGS ratings. Conclusions SCG severity may limit the improvement of patients receiving ECT. Further studies are needed to examine differences based on electrode placement and to determine whether patients with severe SCG may require more ECT treatments in an index course.

Electroconvulsive therapy in the presence of brain tumor. Case reports and an evaluation of risk.

The clinical basis for the long established contraindication of electroconvulsive therapy (ECT) in the presence of brain tumor is reviewed, as is the recent literature that has questioned the absolute nature of that contraindication. A need for a specific estimate of risk is noted. Seven retrospective case reports are added to the 28 cases reported in the literature. The clinical case report data are then pooled and evaluated by outcome. Results indicate a 74 per cent overall morbidity, including a 28 per cent 1-month mortality rate for patients with brain tumors who receive ECT. Twenty-one per cent of the patients had a positive behavioral response to ECT without complication.

The persistence of electroconvulsive therapy-induced changes in the electroencephalogram.

The literature concerning the effects of electroconvulsive therapy (ECT) upon the EEG is reviewed with respect to the degree and persistence of abnormalities. The most common electrophysiological dysfunction consists of generalized regular and irregular slow wave activity. This slowing typically disappears by a few weeks to a few months following completion of the ECT course but in rare cases may persist for longer periods. Patients given large numbers of ECT treatments tend to show more prolonged alterations. Possible correlations of these EEG changes with a variety of parameters are discussed.