Joan Prudic

Effects of Stimulus Intensity and Electrode Placement on the Efficacy and Cognitive Effects of Electroconvulsive Therapy

BACKGROUND The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain. METHODS In a double-blind study, we randomly assigned 96 depressed patients to receive right unilateral or bilateral electroconvulsive therapy at either a low electrical dose (just above the seizure threshold) or a high dose (2.5 times the threshold). Symptoms of depression and cognitive functioning were assessed before, during, immediately after, and two months after therapy. Patients who responded to treatment were followed for one year to assess the rate of relapse. RESULTS The response rate for low-dose unilateral electroconvulsive therapy was 17 percent, as compared with 43 percent for high-dose unilateral therapy (P = 0.054), 65 percent for low-dose bilateral therapy (P = 0.001), and 63 percent for high-dose bilateral therapy (P = 0.001). Regardless of electrode placement, high dosage resulted in more rapid improvement (P < 0.05). Compared with the low-dose unilateral group, the high-dose unilateral group took 83 percent longer (P < 0.001) to recover orientation after seizure induction, whereas the combined bilateral groups took 252 percent longer (P < 0.001). During the week after treatment, there was three times more retrograde amnesia about personal information with bilateral therapy (P < 0.001). There were no differences between treatment groups in cognitive effects two months after treatment. Forty-one of the 70 patients who responded to therapy (59 percent) relapsed, and there were no differences between treatment groups. CONCLUSIONS Increasing the electrical dosage increases the efficacy of right unilateral electroconvulsive therapy, although not to the level of bilateral therapy. High electrical dosage is associated with a more rapid response, and unilateral treatment is associated with less severe cognitive side effects after treatment.

The impact of medication resistance and continuation pharmacotherapy on relapse following response to electroconvulsive therapy in major depression

After clinical response to electroconvulsive therapy (ECT), 58 patients with major depressive disorder were followed for 1 year or until relapse. The rate of relapse was substantially higher in patients who had failed adequate antidepressant medication trials prior to ECT than in patients not determined to be medication resistant. Adequacy of post-ECT pharmacotherapy was only marginally related to likelihood of relapse. The subgroup of patients who appeared to benefit from adequate post-ECT pharmacotherapy were those who did not receive an adequate medication trial prior to ECT. The findings call into question the common practice of administering as continuation pharmacotherapy following ECT the same class of medications that patients had failed with during the acute episode prior to ECT. The findings also indicate that resistance to antidepressant medication is a strong predictor of relapse following response to ECT.

The cognitive effects of electroconvulsive therapy in community settings.

Despite ongoing controversy, there has never been a large-scale, prospective study of the cognitive effects of electroconvulsive therapy (ECT). We conducted a prospective, naturalistic, longitudinal study of clinical and cognitive outcomes in patients with major depression treated at seven facilities in the New York City metropolitan area. Of 751 patients referred for ECT with a provisional diagnosis of a depressive disorder, 347 patients were eligible and participated in at least one post-ECT outcome evaluation. The primary outcome measures, Modified Mini-Mental State exam scores, delayed recall scores from the Buschke Selective Reminding Test, and retrograde amnesia scores from the Columbia University Autobiographical Memory Interview–SF (AMI–SF), were evaluated shortly following the ECT course and 6 months later. A substantial number of secondary cognitive measures were also administered. The seven sites differed significantly in cognitive outcomes both immediately and 6 months following ECT, even when controlling for patient characteristics. Electrical waveform and electrode placement had marked cognitive effects. Sine wave stimulation resulted in pronounced slowing of reaction time, both immediately and 6 months following ECT. Bilateral (BL) ECT resulted in more severe and persisting retrograde amnesia than right unilateral ECT. Advancing age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits. Thus, adverse cognitive effects were detected 6 months following the acute treatment course. Cognitive outcomes varied across treatment facilities and differences in ECT technique largely accounted for these differences. Sine wave stimulation and BL electrode placement resulted in more severe and persistent deficits.

Effects of Pulse Width and Electrode Placement on the Efficacy and Cognitive Effects of Electroconvulsive Therapy

BACKGROUND While electroconvulsive therapy (ECT) in major depression is effective, cognitive effects limit its use. Reducing the width of the electrical pulse and using the right unilateral electrode placement may decrease adverse cognitive effects, while preserving efficacy. METHODS In a double-masked study, we randomly assigned 90 depressed patients to right unilateral ECT at 6 times seizure threshold or bilateral ECT at 2.5 times seizure threshold, using either a traditional brief pulse (1.5 ms) or an ultrabrief pulse (0.3 ms). Depressive symptoms and cognition were assessed before, during, and immediately, two, and six months after therapy. Patients who responded were followed for a one-year period. RESULTS The final remission rate for ultrabrief bilateral ECT was 35 percent, compared with 73 percent for ultrabrief unilateral ECT, 65 percent for standard pulse width bilateral ECT, and 59 percent for standard pulse width unilateral ECT (all Ps<0.05 after covariate adjustment). The ultrabrief right unilateral group had less severe cognitive side effects than the other 3 groups in virtually all primary outcome measures assessed in the acute postictal period, and during and immediately following therapy. Both the ultrabrief stimulus and right unilateral electrode placement produced less short- and long-term retrograde amnesia. Patients rated their memory deficits as less severe following ultrabrief right unilateral ECT compared to each of the other three conditions (P<0.001). CONCLUSIONS The use of an ultrabrief stimulus markedly reduces adverse cognitive effects, and when coupled with markedly suprathreshold right unilateral ECT, also preserves efficacy. (ClinicalTrials.gov number, NCT00487500.).

Medication resistance and clinical response to electroconvulsive therapy

We examined the extent to which medication resistance during an episode of major depression was related to short-term clinical response to bilateral electroconvulsive therapy (ECT). Strength of pharmacological treatment trials was rated in 53 patients who met Research Diagnostic Criteria for major depressive disorder and were subsequently treated with ECT. Patients who had failed to respond to adequate pre-ECT pharmacotherapy were substantially less likely to respond to ECT than patients who had not received adequate pharmacological trials before ECT. Therefore, medication resistance had predictive value with respect to the therapeutic effects of ECT. The clinical and theoretical implications of this finding are discussed.

Effectiveness of electroconvulsive therapy in community settings

BACKGROUND Clinical trials indicate that electroconvulsive therapy (ECT) is the most effective treatment for major depression, but its effectiveness in community settings has not been examined. METHODS In a prospective, naturalistic study involving 347 patients at seven hospitals, clinical outcomes immediately after ECT and over a 24-week follow-up period were examined in relation to patient characteristics and treatment variables. RESULTS The sites differed markedly in patient features and ECT administration but did not differ in clinical outcomes. In contrast to the 70%-90% remission rates expected with ECT, remission rates, depending on criteria, were 30.3%-46.7%. Longer episode duration, comorbid personality disorder, and schizoaffective disorder were associated with poorer outcome. Among remitters, the relapse rate during follow-up was 64.3%. Relapse was more frequent in patients with psychotic depression or comorbid Axis I or Axis II disorders. Only 23.4% of ECT nonremitters had sustained remission during follow-up. CONCLUSIONS The remission rate with ECT in community settings is substantially less than that in clinical trials. Providers frequently end the ECT course with the view that patients have benefited fully, yet formal assessment shows significant residual symptoms. Patients who do not remit with ECT have a poor prognosis; this underscores the need to achieve maximal improvement with this modality.

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 seizures 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.

Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes: short-term efficacy and adverse effects.

CONTEXT Medication resistance is the leading indication for use of electroconvulsive therapy (ECT) in major depression. The practice of stopping antidepressant medications prior to ECT derived from studies in the 1960s and 1970s in nonresistant samples. There is also continuing controversy regarding the relative efficacy and adverse effects of right unilateral and bilateral ECT. OBJECTIVE To test the hypotheses that, compared with placebo, concomitant treatment with nortriptline or venlafaxine during the ECT course enhances short-term efficacy without a meaningful effect on adverse effects and reduces the rate of post-ECT relapse, and to test the hypotheses that high-dose, right-sided, unilateral ECT is equivalent in efficacy to moderate-dosage bilateral ECT and retains advantages with respect to cognitive adverse effects. DESIGN Prospective, randomized, triple-masked, placebo-controlled study conducted from 2001 through 2005. SETTING Three university-based hospitals. PATIENTS Of approximately 750 consecutive patients referred for ECT, 319 with a major depressive episode consented, were randomized to pharmacological or ECT treatment conditions, and received at least 1 ECT treatment. MAIN OUTCOME MEASURES Scores on the Hamilton Rating Scale for Depression, remission rate following completion of ECT, and selective measures of cognitive adverse effects. RESULTS Treatment with nortriptyline enhanced the efficacy and reduced the cognitive adverse effects of ECT relative to placebo. Venlafaxine resulted in a weaker degree of improvement and tended to worsen cognitive adverse effects. High-dosage right unilateral ECT did not differ or was superior to bilateral ECT in efficacy and resulted in less severe amnesia. CONCLUSIONS The efficacy of ECT is substantially increased by the addition of an antidepressant medication, but such medications may differ in whether they reduce or increase cognitive adverse effects. High-dose, right-sided, unilateral ECT is at least equivalent to moderate-dosage bilateral ECT in efficacy, but retains advantages with respect to cognitive adverse effects.

Determinants of seizure threshold in ECT: Benzodiazepine use, anesthetic dosage, and other factors

The electrical dosage of the ECT stimulus impacts on efficacy and cognitive side effects, yet seizure threshold (ST) may vary as much as 50-fold across patients. It would be desirable to predict ST on the basis of patient and treatment characteristics. In particular, concerns have been raised that benzodiazepine use and higher dosage of barbiturate anesthetics elevate ST. In a three-site study, ST was quantified at the first ECT session using an identical empirical titration procedure in 294 patients who met RDC and DSM-IIIR criteria for a major depressive episode. ST varied over a 35-fold range across patients treated with right unilateral (RUL) (n = 267) and bilateral (BL) (n = 27) ECT. Higher ST was associated with BL electrode placement (p = 0.001). Among patients treated with RUL ECT, univariate analyses indicated that higher ST was associated with advanced age (p < 0.001), male gender (p < 0.001), greater burden of medical illness (p < 0.001), weight (p < 0.01), duration of mood disorder (p < 0.01), and history of previous ECT (p < 0.05). Average lorazepam dose in the 48 hours prior to ECT was not associated with ST, but was associated with decreased seizure duration (p < 0.01). Absolute, but not weight-adjusted, methohexital dose was associated with ST (p < 0.01). Multivariate analyses in patients treated with unilateral ECT showed that only 27.6% of the variance in ST (p < 0.0001) could be predicted. In the multivariate analyses, only age (p = 0.0001), gender (p = 0.01), and methohexital dose (p = 0.0001) were independently related to ST. Low dosage of lorazepam and methohexital dosage below 1 mg/kg are unlikely to impact on ST. Given the limited capacity to predict ST, empirical titration remains the only accurate method to determine electrical dosage in RUL ECT.

Electroconvulsive Therapy Part I: A Perspective on the Evolution and Current Practice of ECT

The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECTs historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT.