CHPR: Welcome, Dr. Seiner. Can you tell us what led to your interest in electroconvulsive therapy (ECT) and neurotherapeutics?
Dr. Seiner: I went to the University of Michigan and got a degree in chemical engineering, but I decided I didn’t want to fractionate oil for a living, so I went to medical school thinking I would be an internist. While in medical school, I absolutely fell in love with psychiatry, but I had a hard time giving up the white coat. I did a psychiatry residency here at McLean Hospital and then a fellowship in geriatric psychiatry, which included ECT training. There was a big need for ECT, so I stayed on and became the director of McLean’s neurotherapeutics program. Our program has expanded to include TMS, ketamine infusions, and esketamine and is now one of the busiest neurotherapeutics programs in the country.

CHPR: How has the use of ECT changed in the last few years?
Dr. Seiner: ECT is moving away from small, community-based hospitals and toward academic centers and larger programs. Many smaller programs have closed, but academic centers like ours are busier than ever. When I started doing ECT treatments around the year 2000, we performed 2,500 treatments annually, and now we’re doing about 10,000. When you get large enough, you can offer more outpatient ECT, and ECT is moving much more to the outpatient world.

CHPR: Which patients are the best candidates for ECT?
Dr. Seiner: Many severely ill patients, like patients with psychotic depression or catatonia, respond well to ECT. ECT for catatonia works 80%–90% of the time. In psychiatry we don’t have a lot of 80%–90% anything, so I think ECT will be around for a long time because it’s so effective for the most severely ill patients. Also, ECT works well for treatment-resistant depression, schizoaffective disorder, bipolar depression, and delirious mania.

CHPR: For depressed patients, how do you decide whether to use ECT vs TMS?
Dr. Seiner: For moderately to severely depressed but treatment-resistant patients, ECT is still the gold standard, but TMS is a reasonable alternative. Some patients prefer ECT because it works more quickly, but others prefer TMS because they’re scared of ECT or don’t like going under anesthesia. And patients who work might not be able to take the time off for ECT. TMS, in contrast, is very convenient because it’s a half-hour treatment and patients can come during their lunch break or at the beginning or end of the day.

CHPR: Where does ketamine fit in?
Dr. Seiner: There’s a really good case to be made for patients who are severely ill and suicidal to try ketamine first. It’ll either work quickly, within a couple of treatments, or it won’t, in which case they can move on to ECT.

CHPR: Is ECT more effective than ketamine?
Dr. Seiner: Not necessarily; some patients respond better to one, some better to the other. Overall, response rates seem similar, but they’ve never been compared head-to-head. There’s a big multinational study going on, the ELEKT-D study, which is comparing both treatments and is expected to wrap up later this year (Mathew SJ et al, Contemp Clin Trials 2019;77:19–26). However, ketamine is not considered appropriate at this time for psychotic depression, catatonia, or delirious mania. So, we would still send those patients right to ECT, which seems to work well for those illnesses. Active substance abuse is still a concern for ketamine treatment as well, so those patients probably would be better served by ECT or TMS.

CHPR: You mentioned that ECT scares some patients. Is this because of the worry about memory impairment?
Dr. Seiner: That’s the concern that gets the most press. Other people are frightened by the ECT procedure itself. They have disturbing memories of Jack Nicholson in One Flew Over the Cuckoo’s Nest. But many people now, like many in Gen Z, have no familiarity with that movie, so we’re finally starting to be able to put it behind us.

CHPR: That movie unfortunately really stigmatized ECT.
Dr. Seiner: Right, and there’s still a lot of stigma and misinformation, especially on the internet. We have a group here at McLean for anyone who wants to know more about ECT, and it includes people who’ve undergone the procedure. Our philosophy is that we don’t downplay anything; we just want people to see what we do. ECT is a procedure like any other procedure, with side effects and risks, but with a lot of benefits, too. We do everything we can to make it comfortable and minimize the side effects. Kitty Dukakis, the wife of former Massachusetts governor Michael Dukakis, also runs a group here in Massachusetts called “A Light in the Darkness.” It started off as a support group and now focuses on ECT advocacy. These groups help patients feel more comfortable about proceeding with ECT.

CHPR: Can you tell us about recent innovations in ECT?
Dr. Seiner: The biggest change in the field is the way we administer the electrical stimulus. We do a lot more unilateral placement of the electrodes than we did 20 years ago—typically on the right side of the brain, which is the nondominant side for most people—because unilateral placement produces fewer cognitive side effects. We still use other techniques like bitemporal or bifrontal placement of electrodes, but we use them primarily when we’re not getting a sufficient clinical response with the unilateral technique, or when we need a quick response such as with a patient who is catatonic or not eating and drinking.

CHPR: Have there been any other innovations?
Dr. Seiner: We’ve also found that ultra-brief pulses, which are very tiny pulses, produce fewer side effects. Optimal depolarization time of a neuron in the brain is about 0.1–0.2 ms, and the ultra-brief pulse lasts about 0.3 ms, so it’s very close to that, as opposed to the 1 ms that we had been using earlier. A 2008 study showed that the ultra-brief pulses resulted in significantly less retrograde memory loss in patients (Sackheim HA et al, Brain Stimul 2008;1(2):71–83). That finding took the field by storm. All of us sent our machines in to get retrofitted.

CHPR: Do the ultra-brief pulses work as well as the regular pulses?
Dr. Seiner: The ultra-brief pulses are a milder treatment, and about 40%–50% of patients don’t respond fully. For those patients we have to make adjustments, like increasing the pulse width or switching to bifrontal or bilateral.

CHPR: Have there been any other changes?
Dr. Seiner: The other major development is that we’ve learned better ways to prolong ECT’s benefits (Brown ED et al, J ECT 2014;30(3):195–202). The two main options are: 1) a medication regimen to keep people well after ECT; and 2) a slow, gradual taper of ECT to prolong the benefit. With either option alone, there’s about a 50% relapse rate at six months, but by combining them, the relapse rate is lower and the response is often more robust. For example, a study of geriatric patients found that 13% of patients receiving ECT plus medications experienced relapses compared to 20% of patients on medications alone. Also, the patients receiving medications plus ECT remained well for longer durations (Kellner CH et al, Am J Psychiatry 2016;173(11):1110–1118).

CHPR: How long does continuation ECT go for?
Dr. Seiner: Patients usually taper from three times a week to twice a week to once a week. The first month or two after ECT is when the relapse rate is highest, so we watch people closely over that time. If they’re doing well, we taper and discontinue the ECT more quickly, but some patients might require maintenance ECT. Overall we like to follow patients for about six months, but by the end we may be treating them every six weeks or so.

CHPR: What’s the difference between continuation ECT and maintenance ECT?
Dr. Seiner: Continuation ECT lasts for up to six months before we taper off. Maintenance ECT goes beyond six months. Most patients are able to taper it off eventually, but that can sometimes take a year or two in tougher cases.

CHPR: Do any patients continue for longer than that?
Dr. Seiner: Yes, some patients remain in long-term maintenance for years. These tend to be patients with severe and chronic mental illnesses, like schizophrenia, and ECT can really improve their quality of life.

CHPR: You alluded to patients with catatonia earlier; for these patients, how quickly do you see an improvement with ECT?
Dr. Seiner: Catatonia usually is pretty sensitive to ECT, so sometimes after a single procedure you’ll see the patient chatting up the nurses in the recovery room. But often they quickly slip back into a catatonic state, so it can take a few treatments, typically at least five or six, before they really start to improve. You have to be careful with catatonia because patients can look like they’ve recovered but then slide back very quickly, especially if you taper the benzodiazepines too fast.

CHPR: You keep the patients on benzodiazepines when they go for ECT? Don’t the benzodiazepines interfere?
Dr. Seiner: We would love to taper the benzodiazepines, but they are often what’s keeping the patients eating, ambulating, and not completely catatonic between treatments. For young healthy people, young women in particular, their seizure threshold is so low that you can usually produce a seizure even with high doses of benzodiazepines. And if you can’t get a good seizure, you can give flumazenil, which is a benzodiazepine reversal agent, right before the treatment. It’s well tolerated, and many places use it routinely for anybody who’s on a benzodiazepine. We only use it if we absolutely need it in catatonia, because nobody’s studied the effect of reversing benzodiazepines in somebody who’s struggling with catatonia.

CHPR: Can you say a little more about memory loss with ECT?
Dr. Seiner: There are two types of memory loss that we see with ECT. The first type affects anterograde memory, which refers to the ability to store new memories. A meta-analysis found there’s no evidence of any long-term effect of ECT on anterograde memory (Semkovska M and McLoughlin DM, Biol Psychiatry 2010;68(6):568–577). In fact, that meta-analysis found that if you wait a few weeks after ECT, patients do better on cognitive testing after the ECT than they did before. It’s not that we’re making them smarter; it’s just that we underestimate how debilitating depression is on cognition.

CHPR: And what is the second type?
Dr. Seiner: The second type affects retrograde memory. This refers to the loss of ­memories of things that happened before ECT. Some patients lose memories and don’t get them back. The highest risk for memory loss is the period three to four months before ECT, which is also when the patient was most depressed. Those memories are the most vulnerable and sometimes just get lost completely. In rare cases, patients report losing memories from years earlier. These cases of memory loss tend to occur in patients who 1) were very sick for a long time; 2) were on a lot of medications; and 3) went through multiple courses of ECT, particularly bilateral ECT. The most common things that people have trouble remembering—whether it’s within the previous three months or in these rare cases of years in the past—tend to be things they did once and then didn’t really think about again, like a trip, or a restaurant they once went to. Nobody forgets who their daughter is, but they might forget going to their daughter’s piano recital. Of course, some people forget those things even when they don’t have ECT.

CHPR: What do you think of the use of adjunctive medications to minimize memory loss?
Dr. Seiner: There aren’t a lot of data about adjunctive medications, but cholinesterase inhibitors and memantine have been used since they are memory-enhancing agents. The other medication that has some data is thyroid supplementation. We don’t use adjunctive medications because we focus on adjusting how we do the ECT to minimize memory impairment, and we work to optimize patients’ pharmacologic regimen. So far I haven’t been convinced by any of these augmentation strategies enough to implement them regularly.

CHPR: Thank you for your time, Dr. Seiner.