Electroconvulsive therapy (ECT) for mania: Hiding in plain sight

In this issue of Acta Psychiatrica Scandinavica, Popiolek et al. present data on the effect of effect of electroconvulsive therapy (ECT) on time to readmission in patients with bipolar disorder hospitalized for a manic episode.¹ This is yet another high-quality ECT research paper facilitated by the comprehensive patient registries in Sweden, which allow investigation of a myriad of clinical questions at the population level. While their main analysis did not show a difference in time to readmission in patients treated with and without ECT, a subset of patients who had hospital admissions both with ECT and without ECT, showed a trend to longer time to readmission when they had received ECT. As one might expect, patients treated with ECT had more severe lifetime bipolar illness. ECT was administered to patients in 7.3% of 12,337 admissions, which is actually quite a high rate. I suspect that if a similar study was done in the United States, it would be under 1%.

In another recent report using CGI data from a largely overlapping clinical cohort, the Swedish group showed an 85% response rate of mania to ECT, with greater severity of illness associated with higher response.² Indeed, the most important message from both these reports is that ECT is a very effective treatment for acute mania.

ECT is grossly underutilized overall, and particularly in bipolar disorder.^{3, 4} For some reason, it has been difficult for the field to fully embrace the use of ECT for all episode types in bipolar disorder, despite a substantial evidence base supporting its efficacy and safety for these clinical situations. When the US Food and Drug Administration reclassified the ECT device in 2018, it was for catatonia and a severe depressive episode in the context of unipolar or bipolar disorder, but there was no mention of mania.^{5, 6} This is an egregious oversight and the work of our Swedish colleagues with their national register data is an extremely helpful way to bolster the evidence base. Although physicians even in the United States are not technically bound by FDA “cleared indications,” (the FDA does not regulate the practice of medicine, and physicians are free to prescribe ECT as they deem indicated, similar to the “off label” use of medications), it is still reassuring to be able to point to high-quality data for the use of ECT in manic episodes.

Of course, the ECT literature has been replete with such evidence for decades. A PubMed search of “electroconvulsive mania” returns nearly 500 citations; the search “electroconvulsive bipolar” returns nearly 2000. The review article, Electroconvulsive therapy of acute manic episodes: a review of 50 years' experience by Mukerjhee et al. from the American Journal of Psychiatry in 1994 is a classic in the field.⁷ The graphical representation of PubMed citations over time shows a continuously increasing production of articles on ECT for bipolar disorder in recent years. Furthermore, a group of Italian investigators has published data supporting the efficacy and tolerability of ECT for mixed episodes of bipolar disorder, including maintenance ECT.^{8, 9}

Clinically, it is easy to understand why depressive episodes are so much more commonly treated with ECT than manic episodes. Most manic episodes can be successfully managed with adequate mood stabilizing and sedating medications. Typically, ECT is only considered for severe manic episodes, and when multiple medications trials have been inadequately helpful.

The complicating factor of obtaining fully informed consent from an acutely manic patient only adds to the restricted use of ECT in such situations.¹⁰ The rare, and most severe, form of mania, delirious mania, is an urgent medical situation, and one in which timely application of ECT may be life-saving.¹¹

What about technical aspects of ECT for manic episodes? Popiolek and colleagues report that about half of the patients in their analysis received right unilateral (RUL) ECT; they noted this as a potential limitation, suggesting that the high ECT response rates they reported might have been even higher, had more patients been treated with bilateral electrode placement. Given that acutely manic patients considered for ECT are typically extremely ill, it seems reasonable to consider offering them the form of ECT that is most likely to be rapidly effective. The treatment of acute mania is often a situation in which considerations of efficacy should take precedence over tolerability concerns about temporary cognitive effects. On the other hand, the excellent results from the ECT used in Sweden, as well as earlier data in the literature, could be argued as evidence for the suitability of RUL ECT, even for acute mania.^{12, 13} On balance, I believe the clinical wisdom that the more urgent the situation, the more appropriate the use of bilateral ECT is, should still prevail.¹⁴

Real-world experience, backed by a very substantial evidence base in the literature, argues for the continued acceptance of ECT as a standard treatment (usually secondary, when medications have failed, but also rarely as a first-line (primary) treatment in urgent situations) for all types of mood episodes in bipolar disorder: depressed, mixed and manic. These new data from the Swedish registries are an important addition to that literature. That the FDA considered this evidence base, as well as that for ECT in schizophrenia, insufficient to grant an indication, seems like an oversight or outright mistake. No matter, though, clinicians worldwide can reassure their patients that there is plenty of evidence and experience of ECT as an effective and safe treatment for all types of episodes in severe bipolar disorder.

Dr. Kellner receives fees from UpToDate for writing/editing ECT topics, royalties from Cambridge University Press for Handbook of ECT (2019), and fees from Northwell Health for teaching in an ECT course.