Unilateral ECT Equal to Bilateral Approach for Major Depression

Nancy A. Melville

March 02, 2016

Twice-weekly high-dose unilateral electroconvulsive therapy (ECT) for severe depression is as effective as bilateral ECT, with fewer cognitive side effects, new research shows.

"In line with previous efficacy trials, we found in a real-world setting [that] high-dose unilateral ECT retains some of its cognitive advantages," senior author Declan McLoughlin, PhD, of Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland, told Medscape Medical News.

The study was published online February 19 in the American Journal of Psychiatry.

Pragmatic Trial

Although ECT is considered the most effective treatment for refractory, severe depression, side effects, particularly retrograde amnesia, are among key concerns that can limit use of the treatment.

Efforts to reduce these negative effects have included unilateral electrode placement, which has been linked to fewer side effects than the more common bilateral approach. However, research indicates that the unilateral approach is less efficacious.

The investigators compared unilateral ECT with bilateral ECT in a noninferiority trial in a routine clinical practice setting. They enrolled patients who had been been diagnosed with major depression to receive either twice-weekly moderate-dose (1.5 times seizure threshold) bitemporal ECT (n = 69) or twice-weekly high-dose (6 times seizure threshold) right unilateral ECT (n = 69).

The mean age of the participants was 56.7 years, and 63% were women. Patients receiving antidepressants continued with their therapy.

Posttreatment measures of depression, rated by use of the 24-item Hamilton Depression Rating Scale, showed that the high-dose unilateral approach was noninferior to bitemporal ECT (mean difference, 1.08 points in favor of unilateral ECT).

Further follow-up 6 months post treatment showed no significant differences between the two groups with respect to response or remission.

The unilateral group experienced faster recovery of orientation following the ECT treatment (median, 19.1 minutes vs 26.4 minutes for bilateral), as well as better verbal learning.

Importantly, percent recall of autobiographical information that persisted for 6 months was lower in patients in the patients receiving bilateral ECT (odds ratio = 0.66).

There were no significant differences between the two groups with respect to physical side effects or serious adverse events.

The mechanisms behind the reduced cognitive effects seen with unilateral right ECT are not well understood. It has been speculated that the brain's left hemisphere and memory play a role, Dr McLoughlin said.

"It is possibly something to do with the initial stimulus electrical charge not directly affecting the left dominant hemisphere and, in particular, structures within, such as the hippocampus, that are important for memory function."

Dr McLoughlin noted that there were no baseline differences that were associated with better or worse outcomes.

"This suggests that there may well not be any major clinical factors that are going to predict a better response to bitemporal than to high-dose unilateral ECT and vice versa. However, we should be cautious here because the trial was not specifically designed to test this."

The authors note that the overall remission rate in the study (44.2%) was lower than the rates reported in some trials (range, 46% to 65%) and was similar to that reported in a large community study (46.7%). The overall 6-month relapse rate (31.1%) was lower than was reported in a recent meta-analysis, which Dr McLoughlin and his team also published.

"These differences most likely reflect the pragmatic nature of our trial, in which the number of treatments was decided by the patients and referring physicians rather than by the protocol, as well as a naturalistic follow-up, and are unlikely to be related to concomitant use of antidepressants, which may improve ECT efficacy," the authors note.

Memory Tough to Assess

Commenting on the findings for Medscape Medical News, Laura J. Fochtmann, MD, professor of psychiatry, pharmacologic sciences, and biomedical informatics, Stony Brook University School of Medicine, in New York, noted that an important aspect of the study is the twice-weekly use of ECT, which is common outside of the United States, as opposed to the thrice-weekly approach typically used in the United States.

"It is useful to know that the findings are similar when ECT is given twice weekly as with three times per week administration," she said.

The response and remission rates, which were lower than those reported in other ECT studies, are also notable, she said.

"There may be a number of reasons for this, but it is possible that giving ECT twice weekly rather than three times a week contributed," Dr Fochtmann said.

She added that a potential limitation of the study is that autobiographical memory can be particularly difficult to assess accurately under many circumstances, even in individuals without depression.

"The consistency of memory can change over time in individuals who haven't received ECT," she noted.

"Although the study shows there is a statistically significant difference in the change in this measure between the individuals who received unilateral as compared to bitemporal ECT, it is difficult to determine how the magnitude of this change compares to the expected loss of memory consistency over time in a normal individual or in a depressed person who has not received ECT."

The study was supported by the Health Research Board. Coauthor Sabine Landau, PhD, has received salary support from the NIHR Biomedical Research Centre, the Maudsley NHS Foundation Trust, and King's College London. Dr Fochtmann has disclosed no relevant financial relationships.

Am J Psychiatry. Published online February 19, 2016. Abstract

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