This study demonstrated that the use of an ultrabrief pulse in ECT results in more efficient electrical stimulation than a traditional brief pulse. Further, ultrabrief pulse stimulation markedly reduces the acute, short-term, and long-term adverse cognitive effects of the treatment. This study confirmed that at high dosage relative to seizure threshold, RUL ECT administered with a traditional brief pulse does not differ in efficacy compared to a form of high dosage bilateral ECT, but retains advantages with respect to the acute recovery of orientation and short- and long-term retrograde amnesia. However, ultrabrief RUL ECT, administered at a high dosage relative to threshold, showed robust therapeutic effects, not differing from the traditional brief pulse conditions in any efficacy measure, including potential for relapse. Patients receiving this form of treatment did not show deterioration in any cognitive measure relative to baseline when assessed during and immediately following the treatment course or at long-term follow-up. Patients receiving this treatment also reported that the subjective impact of ECT on memory was less adverse than patients in each of the other conditions. Thus, the use of an ultrabrief stimulus coupled with high dosage RUL stimulation is a strategy that appears to retain the therapeutic properties of ECT, while substantially reducing its potential for adverse cognitive side effects. The option of ultrabrief stimulation is now standard with the ECT devices produced by the two US manufacturers, and, in some cases, can be implemented as an upgrade to older devices.
Retrograde amnesia for information about one’s life is the best-documented long-term adverse effect of ECT, and is typically reported by patients as the most distressing aspect of the treatment. This study used an instrument especially sensitive to this type of amnesia, with 118 questions about autobiographical events.4, 11, 26
The differences among the treatment groups in retrograde amnesia at the 6 month follow-up were statistically robust and of clinical significance (). The patients treated with BL brief pulse ECT, whether as a first and only course or as crossover treatment, could not recall any information or gave inconsistent responses to more than 22% of the questions they answered at baseline. These error rates were 10%, 6%, and 6% in the groups treated with RUL brief pulse, BL ultrabrief, and RUL ultrabrief ECT, respectively. Thus, the magnitude of long-term retrograde amnesia is a function of treatment technique.
For decades it had been assumed that the efficacy of ECT depended on the elicitation of the generalized seizure, while the cognitive side effects were also sensitive to electrical parameters.37, 38
The demonstrations that the efficacy of RUL ECT is contingent on electrical dosage contradicted this view and showed that generalized seizures could be reliably produced that lacked efficacy.5, 11–13
In this study, BL ECT administered with an ultrabrief stimulus at 2.5 times the initial seizure threshold had inferior efficacy. It is unlikely that this effect was due to imbalances among the groups in baseline characteristics. Neither psychotic depression nor history of prior ECT was associated with clinical outcome, whether or not statistically controlling for treatment condition (data not shown). The imbalances likely reflected the large number of comparisons of the treatment conditions in baseline characteristics. Indeed, this loss of efficacy for BL ECT had been observed in earlier attempts to use ultrabrief stimulation to minimize electrical dosage.39, 40
It is likely that with ultrabrief stimulation, electrical dosage relative to seizure threshold also impacts on the efficacy of BL ECT, and in this study the dosage 2.5 times the initial seizure threshold was insufficient to maintain therapeutic effects.
Of course, the reason why the efficacy of BL ECT would be undermined at these parameter settings is matter of considerable interest. It should be recognized that the marked reduction in pulse width changed the size and geometry of the population of neurons engaged in the ictal process. The use of a 0.3 ms pulse did not result in a 5-fold gain in efficiency in seizure induction with either BL or RUL ECT, but rather an impressive gain of 3–4 fold. Since the amplitude of the pulse falls off with distance from the surface stimulation, the traditional wide pulse width was intrinsically more likely to trigger depolarization from a larger population of neurons. The size and location of the population of neurons engaged in the ictal process and the local intensity of the ictal discharge may be critical efficacy. We have long suggested that the seizure triggers an anticonvulsant response that, in terminating the seizure, also is responsible for the antidepressant properties of the treatment.41
RUL ECT has a considerably lower seizure threshold than BL ECT, suggesting less shunting of current. This fact, and the use of a markedly suprathreshold stimulus with RUL ECT, may have protected its efficacy when using an ultrabrief stimulus as a sufficiently large population of neurons may have been engaged in the ictal process, thus resulting in the anticonvulsant response needed to exert maximal therapeutic benefit. Had the dosage of the ultrabrief BL ECT condition been substantially increased, it is likely that efficacy would have been preserved.
Regardless, enhancing the efficacy of ultrabrief BL ECT through increased electrical dosage has doubtful clinical utility. Such an increase should only intensify an already inferior side effect profile compared to ultrabrief RUL ECT. Even though ECT results in a generalized seizure, manipulations of electrical parameters profoundly impact on safety and efficacy. This should also be the case with forms of brain stimulation that do not result in seizures, e.g., deep brain stimulation (DBS), transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS). It is noteworthy that, due to safety issues, the widest pulse width used with these modalities is 0.5 ms, while wider pulses have been routine with ECT. It may be a general principle that restricting the pulse width of stimulation to the range close to the chronaxie for depolarization is critical in minimizing the side effects of any form of brain stimulation. Indeed, this study contrasted the use of a “traditional” 1.5 ms pulse width with a 0.3 ms ultrabrief pulse. The 1.5 ms pulse was especially wide and had the comparison with ultrabrief stimulation been made to a 1.0 ms pulse, as widely used in clinical practice, it is likely that the effects on cognitive measures would not have been as dramatic. This possibility only underscores the fact that basic principles of the physiological and behavioral effects of brain stimulation need to be proposed and verified, and parameter optimization carefully determined. It is of considerable practical and theoretical interests why reducing pulse width to a duration closer to that optimal in producing neuronal depolarization had such a dramatic effect on cognitive measures. We might speculate that with the repetitive pulses given in ECT, there is largely synchronous depolarization of the large population of neurons needed to produce a self-sustaining seizure. Consequently, increasing pulse width is an especially inefficient strategy for seizure production. Further, stimulation during the refractory period following depolarization may have biological effects distinct from stimulation that has yet to result in depolarization.
Undoubtedly, the findings of this study will raise considerable debate about the optimal algorithm in the use of ECT in mood disorders. The findings strongly support initial use of high dosage ultrabrief RUL ECT. However, some patients will show poor or slow response to this intervention. There is insufficient information to decide at this point whether subsequent treatment should involve an increase of dosage of the ultrabrief RUL stimulus, a switch to a traditional pulse width with high dosage RUL ECT, or a switch to some form of BL ECT. Previous reports from our group have shown long-term differences between BL and RUL ECT in the extent of retrograde amnesia.5, 6
This was also the case in this study with the measures obtained immediately and two months following the ECT course. Nonetheless, the effects of the pulse width manipulation were more profound than the effects of electrode placement at all time points and for most cognitive measures.
The findings of this study also demonstrate that the therapeutic and cognitive effects of ECT are dissociable. In general, correlational studies have not found associations between the extent of amnesia and the therapeutic effects of ECT.2, 4
This is the first study to show that a form of ECT can result in both superior efficacy and less cognitive disturbance than other types of ECT.