Eighty Years On, the Debate Over Electroconvulsive Therapy Continues

John Watson

October 10, 2019

At this past May's annual meeting of the American Psychiatric Association, a protest was underway outside of San Francisco's Moscone convention center. Members of the Citizens Commission on Human Rights, a group founded by the resoundingly anti-psychiatry Church of Scientology, flashed signage and chanted through bullhorns calling for a ban on electroconvulsive therapy (ECT), a decades-old treatment for psychiatric illness.

The image that these protesters probably had in mind is one of barbarism. For many, ECT's reputation is more punitive than therapeutic, with its mid-20th century record of misuse as a disciplinary tool in mental hospitals and a "cure" for homosexuality. Think Jack Nicholson in One Flew Over the Cuckoo's Nest, a film once described as doing for ECT what Jaws did for sharks.

However historically accurate this may be, most modern-day psychiatrists and ECT advocates consider it an anachronism, about as relevant to modern psychiatric practice as mid-20th century heart surgery techniques are to contemporary cardiology. Due in large part to advances beginning in the late 1970s, ECT has successfully reemerged as what many consider the most-effective therapy in all of psychiatry, especially in treatment-resistant depression.

Yet, legitimate concerns exist regarding the risk-benefit profile of this treatment, particularly as it relates to the possibility of long-term cognitive impairment. These have ensured that, more than 80 years after its discovery, ECT remains a point of contention, not just at the fringes but among some of those who know it most intimately.

Reembracing ECT

In the early 1980s, ECT was very much in retreat, the dual result of past controversies and the rise in antidepressant use. As Mary Cregan writes in her recent memoir, The Scar: A Personal History of Depression and Recovery, "In the hospitals that still did provide ECT, it was often used only after a long drug trial had failed."

Cregan's was such a case. In the wake of the death of her first child, she was diagnosed with melancholic depression with psychosis. She was hospitalized in 1984 after a second attempted suicide and did not respond to antidepressant medication. Faced with an entrenched disease and a dire prognosis, she and her doctors decided to proceed with a course of bilateral ECT. She credits this with saving her life.

"I had no access to a feeling of being alive, and I had no hope at all for my future. The suffering was extreme," Cregan told Medscape. "One day after several weeks of treatment, something broke through that monolithic condition of despair. I could feel a sense of possibility, a sense of hope, that I hadn't had access to for a long time."

While practitioners of this era were reluctant to use ECT, researchers were not as willing to abandon a breakthrough treatment for serious psychiatric illness.

"What we've done since the late 1970s is try to personalize the treatment," explained Joan Prudic, MD, medical director of the ECT Service at NewYork-Presbyterian Hospital, Columbia campus.

During that time, ECT practitioners moved away from continuous—or sine-wave—stimulation, with its limited clinical benefits and substantial cognitive side effects, to brief-pulse and later ultra-brief stimulation, which improved side-effect profiles and posttreatment recovery. Electrode placement changed from being predominantly bitemporal to the more focal right unilateral treatment, which achieves similar efficacy with fewer cognitive side effects, as shown in a 2016 randomized study and a 2017 meta-analysis. Crucially, researchers moved from fixed dosing to one based on individual patient thresholds, applying incremental repeated stimulations to determine the lowest possible dose needed to induce seizure.

According to Charles Kellner, MD, chief of ECT at New York Community Hospital in Brooklyn, more than 60% of ECT in the United States is now done on a completely outpatient basis, with a stimulus lasting less than 8 seconds inducing a seizure lasting under a minute.

"A patient comes in to the hospital, has their treatment, leaves in about 90 minutes, and goes about their business," Kellner said. "It's really a very simple, nontraumatic experience for the vast majority of patients."

Life as a 'Rare' Side Effect

For those who have experienced significant long-term cognitive side effects from ECT, the picture is decidedly more complex.

In the early 2000s, Sue Cunliffe was a practicing pediatrician from the United Kingdom and a mother of three young children. She was also in a two-decade-long marriage she describes as coercively abusive. She was prescribed antidepressants to treat the psychological fallout. The medication caused manic episodes and she was diagnosed with treatment-resistant depression. She became suicidal.

The decision was eventually made to administer ECT. From 2004 to 2005, she underwent two courses of bilateral ECT at increasing doses.

She reported adverse outcomes almost immediately. Eventually, the cognitive impairment swallowed up large portions of her life, leaving her unable to practice medicine at age 38, and damaging her vocabulary, memory, and coordination.

"I couldn't even walk through a door without walking into the frame," Cunliffe told Medscape. "But the worst part was that I didn't know [why] I always walked into a door frame."

She described a grueling 2-year period of trying to get a medical practitioner to take her complaints seriously and offer her a diagnosis, which eventually came from a neuro-psychologist. Within 6 months, she was off all medication and beginning a slow road to what is still only a partial recovery. "I just needed to get out of my abusive relationship. If I'd had the counseling, I would never have had ECT."

Cunliffe noted that her case was emblematic of "poor and dangerous practices that are putting patients at risk." She stated that her practitioners failed to adhere to the 2003 guidance on ECT from the UK's National Institute for Health and Care Excellence. This document states that patients must receive full and appropriate information about the risks of treatment during informed consent. Cunliffe said she was warned of the risks of anesthesia, headache, and short-term memory loss only after three to four treatments. The guidance also states that treatment should be stopped when side effects occur and should be administered by professionals trained in its delivery. Her medical records indicate that the treatment, and its increasing doses, were probably administered by an unsupervised junior doctor.

Cunliffe underwent ECT at a time when ECT's beneficial modifications were still not uniformly applied. In a 2007 prospective study, Sackeim and colleagues reported that immediate postoperative and 6-month cognitive outcomes varied considerably in 347 patients depending on where they underwent ECT. Patients who underwent treatment at facilities that still used bilateral treatment and sine-wave stimulation experienced more severe and persistent deficits.

There still appears to be a wide variation in how ECT is administered depending on where patients receive it. A 2012 analysis of contemporary ECT practices (since 1990) observed that many countries still employ it without anesthesia and using sine-wave stimulation. The strides made in modifying ECT may seem apparent, but they are clearly not universally applied.

Why Is 'The Most Effective Treatment in Psychiatry' a Last Resort?

For those administering ECT on a daily basis, the results speak for themselves.

"There really is no more effective treatment in psychiatry than ECT," said Prudic. "The efficacy rates are above 50%, even above 70%, for major depression, which represents the most common diagnosis for which ECT is used."

Yet ECT is still considered by many a treatment of last resort. This is despite the fact that antidepressant use in nonpsychotic major depressive disorder comes with notably diminishing returns, with remission rates of just 13% in patients who have not responded to two previous treatments. Conversely, ECT alone and in combination with pharmacotherapy has been shown to reduce symptoms of depression and short-term psychiatric inpatient readmissions. A 2018 healthcare economic analysis concluded that ECT should be considered after failure of two or more lines of pharmacotherapy or psychotherapy. The authors estimated that, over 4 years, ECT could reduce time with uncontrolled depression from 50% to 33%-37% of life-years.

Data suggest that despite the reported efficacy, there is clear hesitation around ECT use. A 2017 study found that the treatment was administered to just 1.5% of psychiatric inpatients with severe affective disorders.

According to Stephen M. Strakowski, MD, acting senior associate dean for research and associate vice president at Dell Medical School in Austin, Texas, the relative underuse of ECT is probably due in part to persistent stigma, but also to issues of access.

"It's hard to get, especially compared with modern antidepressants, most of which are easy, once-a-day prescriptions," he said. "You have to overcome logistical inertia to get someone scheduled."

As such, several patients come to ECT themselves, rather than through practitioner referral.

Michael S, 73, struggled his whole life with depression and bipolar disorder, which had required hospitalization, before taking it on himself to research possible treatments, which led him to ECT.

"In the beginning, I was having two or three treatments a week," he said. "By the end of the second or third week, I began to feel better. Slowly but steadily I did come out of the depression."

He says he still has mild but manageable depression and hasn't experienced a manic episode in the past 2 years. He does not suffer from any major memory loss after what he estimates to be close to 100 treatments overall.

He sees calls to ban ECT as inhumane. "The bottom line is that it works. To remove vital treatment like this would be a crime, really."

The Debate Over ECT

To Kellner, published results and patient testimonials such as these largely nullify the idea that the benefits of ECT, when used for the right patients, are open to dispute.

"There is no debate in medical and clinical circles about the efficacy and safety of ECT," he said.

An actual debate did take place, however, in September of last year at King's College London. Arguing against the use of ECT was John Read, PhD, a clinical psychologist at University of East London, who told Medscape that his concerns with ECT began to arise in the 1970s, while working as a psychiatric nursing aide at Bronx's Montefiore Hospital, attending to patients immediately after they received therapy at . His concerns have only grown since.

To make the point that ECT lacks efficacy, Read cited two systematic literature reviews he coauthored in 2010 and 2017, assessing available publications comparing ECT with placebo. The reviews analyzed publications before and after 2009, respectively. The most recent review concluded, "There is still no evidence that ECT is more effective than placebo for depression reduction or suicide prevention."

Those arguing on the "pro" side of the debate wrote that Read's analysis was flawed, including "studies of questionable validity on an ad hoc basis." They noted that a 2003 systematic review published in The Lancet found that ECT had a significantly greater short-term efficacy than simulated ECT or pharmacotherapy in depressive disorder. This finding was echoed by separate meta-analyses published that same year and in 2004. Several stand-alone studies conducted this decade have also reported the superiority of ECT over pharmacotherapy, although the difference in remission rates between the approaches is less clear.

There is a relative paucity of randomized controlled trials comparing ECT with placebo, and meta-analyses often rely on a number of historical trials published between the 1960s and 1980s. However, Kellner disputes that this is a limitation, noting that ECT's historical evidence is so incontrovertible that placebo-controlled trials would be unethical in most situations. As noted in reader response to the published debate, it is difficult to imagine an ethically designed placebo-controlled trial whose endpoint is suicide.

Read further contends that ECT's effects, when observed, are highly transient. ECT can act rapidly in those with major depressive disorder, with over 60% of patients experiencing remission at or by week 3 of therapy. Sustaining these effects is difficult, however, and the majority of patients experience a relapse within 6 months of undergoing ECT. There is room for improvement, but Kellner also contends that it is prejudicial to call ECT a short-term treatment.

"ECT treats the current episode of mood disorder, and it treats it better and more thoroughly than any other treatment. The fact that patients get sick in the future has nothing to do with the ECT; it's because mood disorders are lifelong recurrent illnesses."

One of the last points of the debate is also among the most contentious: that ECT causes "brain damage," as Read posits, in a manner similar to severe stress or injury.

"That term is only used by the anti-psychiatry forces," said Kellner. "ECT does not cause brain damage. And the latest neuroimaging data actually show that ECT is brain-restorative rather than -damaging."

The mechanism by which seizures promote efficacy has long been unclear. However, recent imaging data are bringing this into greater focus. A small pilot study conducted in 18 patients with depression was able to predict with approximately 80% accuracy which patients would respond to ECT. Its results also highlighted the importance of the brain's visual network in depression and how ECT may positively intervene in this process.

"In the depressed state, the connectivity changes, people become much more preoccupied with their internal thoughts, and the brain is much less affected by external stimuli, especially the visual inputs," explained coinvestigator Daniel C. Javitt, MD, PhD, director of the division of experimental therapeutics at Columbia University Medical Center/New York State Psychiatric Institute. "As a function of ECT, the brain remodels. You become much more driven by external stimuli and have much less connectivity in the mind-wandering areas of the brain."

Efficacy at What Cost?

All of the ECT practitioners and psychiatrists contacted for this article agreed that the treatment's efficacy was not in question. The more divisive issue, and the one that the field of psychiatry wrestles with to this day, is whether this efficacy comes at the cost of permanent memory damage and cognitive impairment. And if so, how common are cases like Sue Cunliffe's?

Here, too, the debate hinges on a comparison of studies. The first large-scale, prospective study of objective cognitive outcomes, published in 2007, noted that 12.4% of patients treated with ECT had marked and persistent retrograde amnesia at 6-month follow-up. Further analysis revealed that this was significantly more common in those undergoing bilateral rather than right-unilateral ECT.

By comparison, the doctors supporting ECT in the debate cited a 2010 study's conclusion that memory and executive function impairments are largely short-term and occur within the first 3 days post-treatment. By 15 days, key measures of function, like memory and processing speed, had actually improved over baseline levels.

There are additional confounding factors. Depression is reported to negatively and persistently affect memory. Obtaining pre-depression baseline cognitive levels to compare against is difficult, and many historical studies incorporate patients who have undergone forms of ECT that may no longer be in practice.

According to Strakowski, if anything close to a rapprochement is to occur between advocates and critics, it will require longitudinal studies assessing these outcomes in patients long after the traditional 6-month window that most studies have employed.

"Many psychiatrists say that [permanent long-term memory loss] is very rare, but I don't think that's been proven," he said. "All we know is that it does happen. I don't think we really know how often, and that's the scary thing for people."

Strakowski agrees that practicing psychiatrists generally know a lot less about the cognitive side effects of long-term recurring maintenance therapy, and that "longitudinal outcome work is where the field needs to go to continue to improve our understanding of what happens." However, he also noted that this is traditionally among the research that is most difficult to get funded. Disentangling these side effects from those of anesthesia, depression, and the natural cognitive deficits experienced by older patients presents additional obstacles, he added.

Although she spoke alongside the psychologist Read at the King's College debate, Cunliffe finds the distinction of being "for" or "against" ECT overly simplistic. What she wants is a serious inquiry into cases such as hers.

"I'm not saying ban ECT," Cunliffe said. "We have to learn from our mistakes in medicine, and it's okay. If we didn't start new treatments, we'd never find cures. But if you start a treatment and side effects become obvious, then it's the duty of all doctors to start informing people of this."

Building on, Not Abandoning, ECT

In recent years, researchers have begun to investigate treatments that may mimic ECT's effects via noninvasive approaches without inducing a seizure, like transcranial magnetic stimulation and transcranial direct current stimulation.

"Within the next 10-15 years, there should be techniques that are just as efficacious but with much fewer side effects," said Javitt.

The emergence of ketamine as an effective therapy for treatment-resistant depression offers additional promise.

According to Joshua A. Berman, MD, PhD, assistant professor of psychiatry at Columbia University Irving Medical Center, what is clear is that, despite its limitations, we are far from being done with ECT.

"There probably need to be parallel tracks," Berman told Medscape. "One is to develop some of the other techniques to the point where they can equal ECT in efficacy, and then at the same time to better understand and control the risks of ECT."

Strakowski hopes for new psychiatric treatments as well, but he does not find the evidence substantial enough to move the needle for patients with more serious depression.

"My view is that the best thing we can do in our specialty is keep as many options open as possible," he said. "Unless there's a specific, serious, and common recurring risk, why would we not want to have this treatment available?"

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John Watson is a freelance writer.

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