Michael E. Henry, MD

included a Point/Counterpoint feature on electroconvulsive therapy (ECT). You can read the introductory essay, “Electroconvulsive Therapy: Obsolete and Dangerous or Still Just Misunderstood?” by Horacio A. Capote, MD, 

 have agreed to continue their debate online. Ms. Hancock, Cunliffe, and Dr Read argue that ECT is 

. Representing the pro-ECT position, Dr Henry has responded to their article below.

I would also like to thank Sarah Hancock, MS, CRC, Sue Cunliffe, MBchB, RCPCH, John Read, PhD for responding to my article “

Their objections to electroconvulsive therapy (ECT) are primarily focused on the cognitive side effects, which they feel are caused by ECT-induced brain damage, and methodologic issues with studies supporting the efficacy of ECT. The main problem with their critique is that they appear to misinterpret the statistics they are presenting.

For example, when they discussed the findings of Peltzman and colleagues, they reported that the study found that ECT patients in the Veterans Health Administration (VHA) were 1.3 times more likely to die by suicide than 

 They failed to appreciate that when the authors compared the ECT patients to a risk-matched cohort, this finding did not meet statistical significance (

=.095), despite the large sample size of 14,810 ECT patients and 58,369 controls. They also failed to mention the authors’ conclusion that the “use of ECT in the VHA is rare. Patients who receive ECT have a complex and high-risk profile …”

 Similarly, Hancock and colleagues cite statistics from Duma and colleagues regarding 

 In their meta-analysis of the major cardiac events, the authors conservatively excluded 28 of 82 studies because they reported no adverse events. Without inclusion of this group the incidence of cardiac deaths and all-cause mortality were 0.18 and 0.33 per 1000 patients, respectively. When this group of studies was included, the incidence of cardiac deaths and all-cause mortality dropped to 0.04 and 0.13 per 1000 patients. They also did not consider that in the Veterans Health cohort, the risk ratio of all-cause mortality for the ECT group was a statistically non-significant 0.88, less than the non-ECT group.

My previous response to the question of whether ECT causes brain damage has already highlighted the findings and conclusions of Gbyl and Videbech, who reviewed 32 imaging studies of ECT with a total of 467 patients and 285 controls. They reported that none of the studies they reviewed found evidence of 

 Hancock and colleagues point to EEG, PET, SPECT, and fMRI data that show relative decreases in the activity of the frontal and temporal lobes after ECT as evidence that ECT causes brain damage.

 They do not appear to have considered the data that show depression is associated with overactivity in these same brain regions.

In addition to failing to present a balanced interpretation of the safety data for ECT, Hancock and colleagues ignore converging lines of evidence that support the efficacy of ECT. For example, they reject a study such as that published by Helle and colleagues, for lack of a 

 In this study, the authors used a randomized parallel treatment design with blinded raters to compare brief-pulse RUL to algorithm-based pharmacology in 73 subjects with bipolar depression. They found a significantly higher response rate of 73.9% for the ECT group versus 35.0% for the medication group (

 = .01). These results are remarkably similar to those of Perugi and colleagues, who treated 522 consecutive patients with treatment-resistant bipolar disorder with ECT and found response rates of 68.1 for bipolar depression, 72.9% for mixed state, 75% for mania and 80% for catatonia.

 To provide some context for these response rates, one of the pivotal clinical trials for the olanzapine/fluoxetine combination treatment for bipolar depression reported a response rate of 56.1% for the active drug versus 30.4% for the placebo treatment arm.

 Although these latter results are from a separate study, the response rates are consistent with other medication studies in this population.

Most importantly, we should not forget that the treatment options for individuals afflicted with severe depression, many of whom actively contemplate suicide frequently, are limited. Hancock and colleagues should apply balanced, rigorous scientific scrutiny to the available data before they advocate against ECT. Their analysis to date has not met that standard.

is the head of ECT and lecturer on psychiatry at Massachusetts General Hospital. He receives salary support from a National Institutes of Health grant on ECT.

1. Henry ME. ECT: an effective and safe treatment. 

2. Peltzman T, Gottlieb DJ, Shiner B, Riblet N, Watts BV. Electroconvulsive Therapy in Veterans Health Administration Hospitals: Prevalence, Patterns of Use, and Patient Characteristics. 

3. Peltzman T, Shiner B, Watts BV. Effects of Electroconvulsive Therapy on Short-Term Suicide Mortality in a Risk-Matched Patient Population. 

4. Duma A, Maleczek M, Panjikaran B, Herkner H, Karrison T, Nagele P. Major Adverse Cardiac Events and Mortality Associated with Electroconvulsive Therapy: A Systematic Review and Meta-analysis. 

5. Gbyl K, Videbech P. Electroconvulsive therapy increases brain volume in major depression: a systematic review and meta-analysis. 

6. Fosse R, Read J. Electroconvulsive treatment: hypotheses about mechanisms of action. 

7. Dale E, Pehrson AL, Jeyarajah T, et al. Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. 

8. Schoeyen HK, Kessler U, Andreassen OA, et al. Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. 

9. Perugi G, Medda P, Toni C, et al. The role of electroconvulsive therapy (ECT) in bipolar disorder: effectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic features. 

10. Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. 

11. Bahji A, Ermacora D, Stephenson C, et al. Comparative efficacy and tolerability of adjunctive pharmacotherapies for acute bipolar depression: a systematic review and network meta-analysis. 

12. Pompili M, Verzura C, Trovini G, et al. Lurasidone: efficacy and safety in the treatment of psychotic and mood disorders. 

Articles

Research data shows that ECT is often more effective than alternative treatments, and safe too. 

In Defense of ECT

The article by John Read, PhD, and colleagues argues in favor of suspending the use of electroconvulsive therapy (ECT) due to a lack of efficacy data and unacceptable adverse effects, specifically, brain damage.

 Unfortunately, the analysis is based on studies conducted prior to the modern era of ECT, and it draws on a limited slice of the available safety and efficacy data for ECT. More recent studies have found key areas of efficacy (

Electroconvulsive Therapy: Obsolete and Dangerous or Still Just Misunderstood?

ECT: Dangerous on Either Side of the Pond

John Read, PhD, Sarah Hancock, MS, CRC, Sue Cunliffe, MBchB, RCPCH

The selection criteria used by Read and colleagues were limited to older studies (1956 to 1985) and critiques of the quality of the data. Thus, the piece is judging clinical trial designs from the 1980s and earlier, using 2019 standards. It is no surprise that the included studies do not utilize methodology developed after the studies were completed. More importantly, the analysis did not include reports that compare different types of ECT, and comparisons of ECT with pharmacotherapy were also not included. This excludes most of the recent meta-analyses and clinical trials of ECT, which have used state-of-the-art clinical trial design. For example, a recent meta-analysis conducted by 

 compared ultrabrief pulse right unilateral (RUL) ECT with brief pulse RUL ECT.

 They found remission rates of 44.9% for brief pulse right unilateral ECT vs 33.8% for ultra-brief pulse RUL ECT (OR, 0.71; 95% CI, 0.51-0.99; P = .045). Their meta-analysis showed that brief pulse caused more cognitive adverse effects than ultrabrief pulse, but there were no data after the acute course.

Table. Key Efficacy Findings From Recent Studies

Since ECT is considered to be an established treatment, it can be used as an active comparator in a noninferiority paradigm, avoiding the ethical dilemma of treating very ill patients with a placebo treatment. As such, Helle K. Schoeyen, MD, PhD, and colleagues 

 brief-pulse RUL ECT to algorithm-based pharmacology in a cohort of patients with treatment-resistant bipolar depression.

 At the end of a 6-week trial, the Montgomery-Asberg Depression Rating Scale scores in the ECT group were 6.6 points lower than those of the pharmacological treatment group (95% CI, 2.5-10.6; P = .002). In a 

, Charles Kellner, MD, and colleagues compared continuation ECT augmented by venlafaxine with lithium plus venlafaxine in geriatric depression.

 At 24 weeks, the ECT group had statistically significantly lower depression scores (Hamilton Depression Rating Scale score, 4.2; 95% CI, 1.6-6.9) than the medication only group. If ECT were not more effective than placebo, as Read and colleagues proposed, there would be no difference in the efficacy of different types of ECT, nor would ECT perform better than standard pharmacology. Taken together, these studies support the acute and sustained clinical efficacy of ECT and are inconsistent with the lack of efficacy proposed by Read and colleagues.

The main safety concern raised by Read and coauthors is that ECT causes brain damage. Specifically, they argued that the changes to autobiographical memory and the memory difficulties reported by patients following ECT treatment are evidence of brain damage. They also cited “microvascular, neuronal, voltage-gated ion channel damage that is visible on standard brain scans” as further buttressing this argument.

 The piece also leverages an article from 1946,

 and the minutes from a traumatic brain injury advisory board meeting8 to support the brain damage claim. However, it does not appear that the more recent studies that fail to show chemical or structural evidence of brain damage with ECT,

 nor those that suggest improvement in cognitive function relative to baseline following ECT.

Perhaps the most interesting finding regarding the memory effects of ECT is that the hippocampal volume, which has been shown to 

 in major depression, increases following a course of ECT treatment.

 This finding has been supported by 2 recent studies. Leif Oltedal, MD, PhD, and colleagues reported results from a multicenter imaging trial of the effects of ECT on hippocampal volume using structural magnetic resonance imaging in 281 patients from the Global ECT-Magnetic Resonance Imaging Research Collaboration.

 Their results showed an increase in hippocampal volume in participants receiving unilateral or bilateral ECT, while the 95 control participants who did not receive ECT did not show changes between the 2 scans.

This finding was corroborated by a systematic 

 of ECT’s effects on the brain’s structure by Krzysztof Gbyl, MD, and Paol Videbech, MD, DMSc.

 They reviewed 32 studies with 467 patients and 285 controls, and drew a number of interesting conclusions. None of the studies they reviewed reported evidence of brain damage. Instead, the studies found that hippocampal volume as well as other cortical and subcortical regions showed increases in volume. The authors noted that the increases in brain volume tended to occur in regions of the brain thought to be involved in the pathophysiology of depression.

 They also reviewed 5 diffusion tensor magnetic resonance imaging studies with a total of 92 patients and 62 controls, and the changes they found indicated increased, not decreased, white matter integrity between the frontal and temporal lobes after ECT. These finding are also consistent with results from a retrospective chart review study by my research group. We were able to identify 100 patients who had received at least 50 ECT treatments, 36 of whom received 100 ECT treatments as part of an acute course of ECT that transformed into maintenance treatment. Cognitive function as measured by the Montreal Cognitive Assessment essentially did not change in either group.

 In short, in an illness thought to result from decreased prefrontal cortical activity and connectivity to limbic structures, there is consistent evidence of increased volume and connectivity, not atrophy, following state-of-the-art modified ECT, which is corroborated by the available cognitive data.

The other safety concerns raised were an increased risk of major cardiac adverse events and an increased risk of death from ECT. While ECT does cause dramatic swings in heart rate and blood pressure, these effects are transient and well known. Further, the swings can be managed with thoughtful pretreatment, assessment, and careful monitoring during the procedure. Consistent with this approach, Niels Tørring, MSc, PhD, and colleagues 

 a systematic review and pooled data analysis from 15 studies and found a death rate of 2.1 per 100,000 treatments.

 This is a decrease from the 4 per 100,000 treatments previously reported.

 Given the population that typically receives ECT, this decline in mortality likely reflects improvements in the medical management of chronic medical conditions and anesthetic technique. These data clearly do not support the assertion of an increased risk of death with ECT.

In summary, the concerns that were raised about ECT are commonly shared by the general public, and they are based on data from older studies that used the methodology now considered outdated both in terms of ECT practice and analytic techniques. Read and colleagues did not consider more recent, state-of-the-art clinical trial data that corroborate more than 75 years of clinical experience supporting the efficacy of ECT in a population of patients who suffer significant disability, increased medical comorbidity, and increased mortality.

1. Read J, Kirsch I, McGrath L. Electroconvulsive therapy for depression: a review of the quality of ECT versus sham ECT trials and meta-analyses. 

2. Tor P-C, Bautovich A, Wang MJ, et al. 

A systematic review and meta-analysis of brief versus ultrabrief right unilateral electroconvulsive therapy for depression

3. Schoeyen HK, Kessler U, Andreassen OA, et al. 

Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment

4. Kellner CH, Husain MM, Knapp RG, et al; CORE/PRIDE WOrk Group. 

A novel strategy for continuation ECT in geriatric depression: phase 2 of the PRIDE study

5. Alpers BJ. The brain changes associated with electrical shock treatment; a critical review. J Lancet. 1946;66(11):363-369.

7. Chen W, Zhongsheng Z, Lee RC. Supramembrane potential-induced electroconformational changes in sodium channel proteins: a potential mechanism involved in electric injury. 

8. Traumatic Brain Injury Advisory Board meeting minutes. California Department of Rehabilitation. August 26, 2019. Accessed February 12, 2021. 

https://www.dor.ca.gov/Content/DorIncludes/documents/TBI/ TBI Full Committee Meeting Minutes 8-26-19.docx

9. Abrams R.And there’s no lasting proof of brain damage. 

10. Weiner R, Reti I. Key updates in the clinical application of electroconvulsive therapy. 

Hippocampal volume changes following electroconvulsive therapy: a systematic review and meta-analysis

Biol Psychiatry Cogn Neurosci Neuroimaging.

12. Oltedal L, Narr KL, Abbott C, et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy. 

Electroconvulsive therapy increases brain volume in major depression: a systematic review and meta-analysis

14. Luccarelli J, McCoy TH Jr, Seiner SJ, Henry ME. Maintenance ECT is associated with sustained improvement in depression symptoms without adverse cognitive effects in a retrospective cohort of 100 patients each receiving 50 or more ECT treatments. 

15. Tørring N, Sanghani SN, Petrides G, et al. 

The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis

16. Abrams R. The mortality rate with ECT. 

There is consistent evidence of benefits following state-of-the-art modified ECT.

ECT: An Effective and Safe Treatment

This book is well-written and concise. It provides an overview of ECT that is evidence-based yet understandable by the average person. The author effectively uses clinical anecdotes to provide a “face” for the science. The book is organized in a user-friendly way.

Patients are most likely to be interested in the first 6 chapters. The remaining chapters complete an overview of ECT that will be more relevant to clinicians.

A brief introductory chapter explains the technology. In the second chapter, the author describes and discusses the patient’s experience. Dr Fink expertly explains in a tone that speaks directly to patients and their families not only what happens during the therapy but also why it happens. This is followed by a discussion of the treatment technique and a review of important issues that the patient and treating physician should discuss during a course of therapy.

A chapter about the effect on memory and the potential side effects of ECT tackles, in a straightforward manner, the most controversial issues that surround this form of therapy. The author succinctly explains how previous limitations in medical practice and technology contributed to a severe impact on memory. Dr Fink then highlights the currently employed advances in medical practice that minimize such adverse effects. The chapters that focus on specific illnesses amenable to ECT address key issues for both patient and clinician.

In the closing chapter, Dr Fink applies current guidelines for ethical behavior by medical practitioners of ECT. He concludes that ECT is ethical and addresses the reality that the suffering caused by bias against ECT is an injustice against patients.

This book is a valuable tool for clinicians and for patients and their families. It is especially helpful for those who are struggling with the decision of whether to proceed with ECT.

Michael E. Henry, MD

Articles

In Defense of ECT

ECT: An Effective and Safe Treatment

Electroconvulsive Therapy: A Guide for Professionals and Their Patients