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Electroconvulsive Therapy: Stayin’ Alive, Stayin’ Well

2021; Wiley; Volume: 144; Issue: 3 Linguagem: Inglês

10.1111/acps.13352

1600-0447

Charles H. Kellner,

Transcranial Magnetic Stimulation Studies

In the current issue of Acta, there are three new publications with data about staying well, or not, in the 6- to 12-month period after successful index courses of electroconvulsive therapy (ECT).1-3 Jelovac et al. show no difference in 12-month relapse rates between patients treated with right unilateral versus bilateral ECT in a secondary analysis of data from the EFFECT-Dep trial; Lambrichts et al. and Methfessel et al. show that withholding maintenance ECT, in both cases an "experiment of nature" imposed by the COVID epidemic, leads to clinical deterioration and relapse in a substantial number of previously stable patients. All three articles focus our attention on the crucial clinical issue of how best to keep patients with serious mood and psychotic disorders well for the long term. It should not need to be repeated in 2021 that ECT is the most effective acute treatment for severe depression and a limited number of other psychiatric diagnoses, but almost all ECT articles (and editorials) start with such a statement, because they still need to.4 ECT is grossly under-prescribed despite decades of compelling scientific evidence of its safety and efficacy.5 This is the result of a complex interplay of factors, among them ongoing lack of knowledge of contemporary ECT technique (including among medical professionals), sensationalist media portrayals, residual stigma from ECT practice decades ago, and, most unfortunately, active campaigns of disinformation promulgated by so-called academic experts with questionable agendas. On a more positive note, ECT practice seems to be holding on to its niche in the treatment armamentarium, because real-world psychiatric patients and their caregivers need it when other treatments do not work, or are not appropriate. ECT is often used as an urgent, life-saving treatment for patients who are dangerously suicidal.6 The hope that more recently developed "brain stimulation" techniques would eliminate the need for ECT has not been realized; no other modality has the proven efficacy in the severely ill population for whom ECT is indicated. The fact that patients relapse after ECT has long been blamed on the treatment itself. This is a shortsighted view that fails to take into account the recurrent nature of mood disorders (or the more continuous natural history of psychotic disorders). In addition, until recently, ECT has been the only antidepressant that was abruptly stopped as soon as the patient responded/remitted. The United States Food and Drug Administration, in its extensive review of the medical literature for ECT that led to the reclassification of ECT devices in 2018, concluded, erroneously, I believe, that there was inadequate evidence for the long-term effectiveness and safety of ECT.7 Disregarding the evidence base for maintenance ECT, the FDA ruling has left many questioning the role of such prophylactic ECT. Continuation and maintenance ECT have become an increasingly important part of contemporary practice, as practitioners strive to prolong the beneficial effects of an acute (or "index") course of ECT. In the case of a severe episode of depression, the goal of an index course of ECT is to treat the current episode, optimally to full resolution. It has become clear that while over half of patients successfully treated with ECT stay well for prolonged periods with various ongoing treatment regimens (pharmacotherapy and maintenance ECT), nearly 40% will relapse, with most of these relapses occurring early on.8 Recognition that pharmacotherapy, while helpful, is not adequate to prevent recurrent illness for many patients has led to the greater utilization of maintenance ECT. The idea of trying to prolong the beneficial brain effects of closely spaced ECT sessions dovetails with the theoretical construct that, despite symptom resolution, a period of vulnerability to relapse into the most recent episode may exist as a biological substrate.9 If the acute brain benefits of ECT (now being elucidated by neuroimaging research10) can be prolonged by additional ECT, spaced at greater intervals, to get past that period of vulnerability, then the patient has a greater chance of remaining in remission. Of course, ongoing prophylaxis will be needed to prevent a possible future episode, if the natural history/biology of the individual's illness is one of recurrence. Thus, maintenance ECT will often be given to well (euthymic) patients; alternatively, in carefully selected patients, it may be possible to wait for early signs/symptoms of recurrence and then quickly administer a treatment to avoid further illness progression. A companion practice to maintenance ECT is the tapering, rather than abrupt cessation, of an index course of ECT. This "continuation ECT" involves a gradual step down from the typical 3X/ week acute ECT schedule, often to twice weekly for a week, then weekly for several weeks, although various schedule protocols exist, and clinician judgment and flexibility are advised.11 The taper period, in addition to sustaining the effects of ECT, allows time for any added pharmacotherapy regimen to take effect, hopefully adding to relapse prevention. In the Prolonging Remission in Depressed Elderly (PRIDE) study, a taper of four additional ECT, at approximately weekly intervals, was successfully incorporated into one of the treatment arms.12 Regarding terminology, Lambrichts et al. choose to refer to all ECT after the index course as “maintenance ECT," avoiding the term “continuation ECT," which has traditionally been used, somewhat arbitrarily, to describe the first six months of treatment after the index course. The combined label "C/M ECT" has also been used and could also be discarded. I applaud this simplification of terminology, as do others in the field (personal communication, Georgios Petrides). Let's just call all ECT after the acute course, “maintenance ECT." Jelovac et al. point out the special place of lithium in relapse prevention, reporting substantially fewer relapses in the nearly half of the cohort on lithium. This benefit is seen even with lower levels of lithium than traditionally used for bipolar prophylaxis; it seems that some lithium is better than none, and lower levels are better tolerated. In the PRIDE study, lithium, in combination with venlafaxine, was well tolerated in a cohort of older patients.12 Lithium should be a strong contender as one of the components of combination relapse prevention pharmacotherapy after a course of ECT, now more commonly combined with maintenance ECT. Further research on optimum pharmacotherapy combination regimens is definitely needed. Finally, the fact that Jelovac et al. showed equal relapse rates with both electrode placements deserves comment. Typically, practitioners continue the same technique (electrode placement, stimulus dose) used in the last index treatment for maintenance treatments (ie, what gets you well, should keep you well). Some practitioners, however, have a different view and believe that the most potent form of ECT (bilateral electrode placement at moderate-high stimulus doses) should be used for maintenance ECT, irrespective of the technique used in the index series, given that the treatments are spaced further apart, and tolerability issues are less of a concern.13 The three articles in this issue of Acta continue the Journal's fine tradition of publishing new data and observations about ECT, according the treatment its rightful place in modern psychiatric medicine. The authors of these articles are to be commended for their careful data accrual, one in a pragmatic research trial and the other two in naturalistic observations of their clinical populations. These data contribute to both the technical refinement of ECT and a better appreciation of the benefits of maintenance ECT. Dr. Kellner receives fees from UpToDate and Northwell Health. He receives royalties from Cambridge University Press.