Abstract
After 80 years, electroconvulsive therapy (ECT) continues to be the most acutely effective treatment available for severe and sometimes life-threatening depression. It’s also a remarkably safe medical procedure with a mortality of 1 per 50,000 treatments (Torring et al., 2017). However, though substantial progress is being made, the best way to administer ECT with regard to optimising therapeutic benefit and simultaneously minimising cognitive side-effects is not yet known.
As described in Rosenman’s Viewpoint article, a group of researchers in Columbia University in New York began systematically assessing this conundrum in the 1980s and made several interesting observations (Rosenman, 2018). These were mainly based upon the notion of ‘seizure threshold (ST)’ being the minimum electrical stimulus dosage required to induce an adequate generalised seizure. For practical purposes, seizure threshold was measured in units of electrical charge, i.e., milliCoulombs (mC). They also noted that inducing a seizure was not in itself sufficient to elicit robust antidepressant effects when using unilateral electrode placement. For unilateral ECT to be effective, it required being administered using a dose substantially above seizure threshold, leading to the current convention of 6 x ST for high-dose unilateral ECT. They emphasised the importance of stimulus dose as a multiple of the seizure threshold rather than the absolute dose employed.
In contrast, bitemporal ECT was effective at doses just above threshold. However, substantially increasing the dose mostly exacerbated cognitive side-effects rather than eliciting any appreciably greater antidepressant benefit. In fact, the earlier Columbia trials using 2.5 x ST, rather than 1.5 x ST, for bitemporal ECT amplified cognitive deficits when comparing bitemporal and high-dose unilateral ECT.
They also reported that seizure threshold was not readily predictable because there was a large, 40-fold, variation in threshold between patients. While technically true, this was a bit of an exaggeration as most of the variation is at the lower end of possible stimulation charges, i.e., 50–200 mC, and much lower for ultrabrief-pulse ECT. For example, in our EFFECT-Dep brief-pulse ECT trial (n = 138), the median threshold was 150 mC for the bitemporal group and 75 mC for the unilateral group with a range of 50–500 mC in both groups (Semkovska et al., 2016). Notwithstanding this, the Columbia group’s take-home message was that it’s better to avoid fixed-dose forms of ECT and risk under/over-dosing patients, and instead attempt to empirically establish each patient’s individual seizure threshold and tailor subsequent treatments to that. For most patients, the seizure threshold can be determined in the first ECT session by titrating upwards from a lower stimulus dose.
Seems not unreasonable? Using this approach, we currently know that high-dose (6 x ST) right unilateral ECT is as effective as moderate-dose (1.5 x ST) bitemporal ECT while having some cognitive advantages regarding recovery of orientation and autobiographical memory (Kolshus et al., 2017). Of note, these advantages are probably lost when going beyond 6 x ST.
Nonetheless, concerns about stimulus titration in ECT practice are intermittently raised, presumably reflecting a sense of unease about this particular method and being advised to follow it (Rosenman, 2018). So which dosing method is best for ECT: a fixed-dose ‘formula’ method based on clinical factors (e.g. ages, sex, electrode position), a more straightforward age-based method (e.g. the patient’s half- or full-age as a percentage of 500 mC) or empirical stimulus dosing? The honest answer is that we do not know for sure because there has never been a high-quality randomised blinded trial to test this issue. What do patients think about this? We don’t know that either.
However, what if you had to take a course of medication for an illness and was offered the choice of having different doses determined by the following: a formula-based fixed dose that may be just fine, too much or not enough; a dose based just on your age that may also turn out to be just fine, too much or not enough; or a dose based upon a strategy that actively adapted to your personal characteristics, was likely to be effective and minimised unpleasant side-effects? What would you choose?
Another concern is that stimulus dosing may add additional treatment sessions (Rosenman, 2018). In the absence of relevant randomised trials, there is very limited evidence to support this conjecture. Despite our own initial concerns that a first low-dose unilateral ECT session to establish the ST would result in a longer ECT course, our own trial and subsequent meta-analysis found no difference in the mean number of sessions (about eight) required between these two forms of ECT (Semkovska et al., 2016; Kolshus et al., 2017). If reducing the number of ECT sessions is a major concern, then one could consider giving it twice-weekly instead of thrice-weekly, which will also help reduce cognitive side-effects (Charlson et al., 2012). Now that’s something our patients might be interested to know.
See Viewpoint by Rosenman 52: 410–414.
