Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy

Abstract

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 P's<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.).

Keywords: Depression; Efficacy; Electrical Stimulation; Electroconvulsive Therapy; Side Effects.

Figure 1

Flow of Participants in the Study.

Figure 2

Seizure Threshold at the Start of ECT. An analysis of covariance was conducted on log-transformed (base10) seizure threshold values, with pulse width and electrode placement conditions and their interaction as between-subject terms and age as a covariate. Seizure threshold was approximately three times higher in patients treated with a brief pulse compared to an ultrabrief pulse stimulus (P<0.001, F = 85.8, df = 1, 85). Seizure threshold was approximately two times higher in patients treated with bilateral compared to right unilateral ECT (P<0.001, F = 32.5, df = 1, 85). The relationship between age and seizure threshold was marginal (P=0.073, F = 3.3, df = 1, 85).

Figure 3

Scores on the Hamilton Rating Scale for Depression Before, During and Following the Treatment Course. A repeated measures analysis of covariance on serial depression severity ratings used pulse width and electrode placement conditions and their interaction as between-subject terms, and age, preECT depression score, and number of adequate medication trials as covariates. In this omnibus analysis depression severity over time varied with the pulse width and electrode placement conditions, as well as their interaction (P’s<0.05). Post hoc analyses indicated that each time point, the ultrabrief bilateral ECT group had inferior outcome relative to the other three groups (P’s <0.05), none of which differed from each other.

Figure 4

Kaplan–Meier Estimates of the Proportion of Patients Who Remained Well One Year after Electroconvulsive Therapy, According to Treatment Group. Survival analyses applying regression models and life-table methods showed no significant differences between the treatment groups (P>0.3).

Figure 5

Scores on the Columbia University Autobiographical Memory Interview. Retrograde amnesia for autographical events was assessed immediately following the end of the randomized and crossover phases and at two- and six-month followup, after completing all ECT. At each time point, Analyses of covariance indicated that each of the ultrabrief ECT conditions resulted in less retrograde amnesia than any of the brief pulse conditions (P’s<0.05). Thus, effects of pulse width on extent of retrograde amnesia persisted at least six month following completion of ECT.