Changing tactics: Does switching improve <scp>electroconvulsive therapy</scp> outcomes?

Electroconvulsive therapy (ECT) is an evidence-based treatment for difficult-to-treat, severe and sometimes life-threatening depressive episodes. Its effectiveness and cognitive side-effects are modifiable by stimulus dose, electrode placement and stimulus pulse width.1 Regarding efficacy, meta-analyses of contemporary randomized controlled trials tell us that brief pulse high-dose unilateral ECT is like brief pulse bitemporal ECT, while ultrabrief pulse high-dose unilateral ECT is less efficacious. However, ultrabrief pulse high-dose unilateral ECT has fewer cognitive side-effects than brief pulse high-dose unilateral ECT, which has less than brief pulse bitemporal ECT.2 In patients showing response to ECT, improvement is mostly witnessed early in the treatment course. In patients not responding after four to six treatment sessions, it is common practice to change the technique, either by switching electrode position, prolonging pulse width, or increasing the stimulus dose. However, remarkably, no high-level randomized controlled trial data are available to robustly support any of these clinical ECT practices or guide when to implement them. Instead, we have some observational data. In this issue, Hart et al. report the results of a large (N = 1699; 59.6% female, 91.8% white), decade-long, single-site, retrospective cohort study, identifying predictors of early and late response.3 The cohort comprised patients who had a moderate–severe unipolar (78.8%) or bipolar depressive episode with a baseline Quick Inventory of Depressive Symptomatology (QIDS) score > 10. Applying various dosing protocols, patients were treated with thrice-weekly ECT, using mostly (94.1%) right unilateral electrode placement with an ultrabrief pulse (0.3–0.37 ms) electrical stimulus. One third (N = 555; 33%) of the patients met the response criterion (i.e., a decrease in QIDS score ≥ 50% from baseline) at treatment number 5, while nearly a quarter (N = 397; 23.4%) responded after treatment number 5. In early non-responders, changing the treatment technique from ultrabrief-pulse to brief pulse (i.e., >0.37 ms) unilateral ECT resulted in a higher likelihood of being a responder as compared to continuing ultrabrief-pulse ECT. This tantalizingly suggests that, for patients being treated with unilateral ultrabrief-pulse ECT, changing the treatment technique is helpful when response is insufficient after the fifth ECT session. The caveat here, of course, is that this was not a randomized controlled trial and therefore is subject to all the biases associated with a retrospective study. Additionally, we do not know what the cognitive effects were of this particular switching tactic. Therefore, there are two main issues here. If a patient is not responding sufficiently, should one switch to a different, more effective, form of ECT but with the potential for more cognitive side-effects? And at what point should this be done, if it were to be done at all? In general, is it even worthwhile adjusting the treatment technique in ECT practice, offering a treatment tailored to the individual patient? About 20 years ago this issue was vividly discussed in the Journal of ECT with Charles Kellner advocating that, in order to raise the global standards of ECT practice, we should focus our attention on the common details of treatment technique that would fit more than 90% of our patients.4 Harold Sackeim and colleagues disagreed, stating that "optimal treatment should be tailored to the needs of individual patients" and that “reverting to a cookbook method is an inappropriate solution to inadequate training in state-of-the-art ECT practice".5 But precisely how should we achieve this laudable goal? Of note, the New York-community ECT study found that, across seven different hospitals that used various ECT techniques and protocols, the antidepressant outcomes of the treatments were actually comparable.6 The technique used seemed mainly to have a differential impact on cognitive side-effects, with more being associated with bilateral electrode placement.7 Assuming that, nevertheless, tailoring is the way to go, how and when can we personalize and adjust a potentially complex treatment like ECT? A fairly large body of evidence is available to make an informed decision as to what electrode position to choose and which stimulus parameters to select.2, 8 There are, however, several possible combinations for these, potentially further complicated by the anesthetic used. To investigate some or all of these would require a series of randomized controlled trials or possibly a large sequential adaptive trial. Of some help is that Hart et al.'s study indicates that switching to brief pulse unilateral ECT is helpful if not meeting a response criterion after five sessions of ultrabrief pulse ECT.3 To provide some further guidance, a network meta-analysis, attempting to provide a ranking of various ECT “protocols” according to their comparative antidepressant efficacy and cognitive side-effect profile, is currently underway.9 One possibility is that we will eventually have a clear hierarchy of switching strategies. Alternatively, the evidence might be to continue with the same initial technique, offering a longer course. In the CORE-studies from the USA, it was seen that of the patients who had an inadequate response after six bilateral ECT sessions, 40% went on to achieve remission after a longer course with the same treatment technique.10 In a recent publication, pooling data from three Columbia University trials and the “Optimization of ECT”-trial, the largest sample of ECT-non-responders were prospectively followed through subsequent treatment. Non-responders went on to receive a second course of ECT, using high-dose bilateral ECT. This second course led to an approximately 70% response rate and a 60% final remission rate. The authors concluded that, since the therapeutic effects were independent of the technique administered in the initial treatment course, it is possible that many patients may benefit simply from longer courses of ECT.11 Timing is everything. When should one switch tactic, or persevere with the form of ECT the course began with, or even discontinue ECT? As Lancaster suggested as early as 1958, one could switch to bilateral ECT in patients “who after six unilateral treatments [are] still being difficult with food and showing other features of depression.”12 In the literature, however, there is a patent lack of consensus about when to change tactics: "after the first few” treatments, after 4, after 5, after 6 or wait until the 10th session. Of course, extending the course of an ineffective treatment has opportunity costs and will also increase treatment risks and side-effects. Hart et al.'s study suggests that it may well be better to decide earlier, rather than later, in the treatment course. It may well be that changing the treatment technique during a course bears little impact on efficacy. Its efficacy remains yet to be demonstrated. Examination of “switching”-strategies represents a relatively straightforward first step. In an upcoming multi-center trial, patients with depression that do not achieve response after four sessions of brief-pulse high-dose unilateral ECT will be randomized to either continue this treatment technique, or change to brief-pulse moderate dose bilateral ECT, with change in depressive symptom severity and cognitive changes as co-primary outcomes.13 Although it will prove hard to further increase the efficacy of a treatment that is as highly efficacious as ECT, trying to optimize efficacy, by speeding up remission while minimizing side-effects, remains a worthy research goal. The peer review history for this article is available at https://publons.com/publon/10.1111/acps.13540.

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