The two top developments of the year in the field of neurostimulation involve the oldest form of the therapy: electroconvulsive therapy, Alexander Sartorius, MD, said at the virtual congress of the European College of Neuropsychopharmacology.
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One of these studies shot down the longstanding notion that ECT causes brain damage. The other, a Danish national registry study, demonstrated that ECT is associated with lower all-cause mortality than in patients with similarly severe depression who don’t undergo ECT.
“The take-home messages are that ECT does not lead to brain damage but rather to a profound gray matter increase. And secondly, ECT lowers all-cause mortality in patients with depression,” said Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.
The year has been less fruitful in terms of research involving deep brain stimulation using implantable electrodes, he continued.
“Basically, one can state that there is no breaking news in the field of deep brain stimulation. DBS remains a highly experimental form of therapy,” Dr. Sartorius said.
ECT-induced brain changes
Investigators participating in the international multicenter Global ECT-MRI Research Collaboration (GEMRIC) reported on the longitudinal effects of ECT on gray matter, white matter, and ventricular volumes in 328 patients who underwent imaging before and after ECT for a major depressive episode, as well as in 95 nondepressed controls.
The key finding was that ECT induced a widespread, nonspecific global increase in gray matter volume. Indeed, the volumetric increase was documented in 79 of 84 gray matter regions of interest. Subcortical gray matter volume increased by a mean of 1.47% in ECT-treated patients, and total cortical volume rose by 1.04%. Total white matter volume remained unchanged.
“The gray matter increase induced by ECT looks quite similar to the gray matter increase seen with physical activity,” Dr. Sartorius noted.
The size of the gray matter volume increase rose with the number of ECT sessions. However, gray matter enlargement in response to ECT showed no relationship with clinical response, indicating that this finding on brain imaging doesn’t have a promising future as a potential biomarker of treatment effectiveness (Biol Psychiatry. 2020 Mar 1;87[5]:451-61).
“The good news from this study is there is no gray matter decrease,” Dr. Sartorius said. “This study enhances the existing evidence falsifying the old idea or dogma that ECT induces brain damage. I would claim that the opposite is clearly the case.”
ECT and mortality
The same group of investigators at the University of Copenhagen who several years ago harnessed Danish national patient registries data to report that ECT was associated with an unadjusted 32% and adjusted 23% reduction in the risk of developing dementia in patients aged 70 years and older (Lancet Psychiatry. 2018 Apr;5[4]:348-56) have recently concluded that ECT was also associated with a 19% reduction in all-cause mortality, compared with that of patients hospitalized for major depression who didn’t receive ECT.
The national registries study included 5,004 patients who were treated with ECT and nearly 88,000 others who were hospitalized for major depression during 2005-2016 but didn’t receive ECT. During up to 11.3 years of follow-up, the risk of all-cause mortality was 8% lower with ECT than with no ECT in patients categorized as having mild depression, 17% lower with a history of ECT for moderate depression, 4% less with severe depression without psychotic features, and 30% less with ECT than no ECT for severe depression with psychotic features (J Psychopharmacol. 2020 Mar;34[3]:273-9).
ECT was associated with an adjusted 6.99-fold increased risk of suicide in patients with mild depression. At first look that’s unsettling, Dr. Sartorius said, but he pointed out that the size of the ECT-associated suicide risk lessened with increasing severity of depression, and in fact, there was no increased suicide risk with ECT in severely depressed patients with psychotic features. ECT was also associated with significantly higher rates of psychiatric rehospitalization, emergency department visits, and suicidal behavior in patients classified as having mild or moderate depression. Dr. Sartorius suspects these findings reflect diagnostic uncertainty surrounding the milder forms of depression, coupled with the reality that ECT is generally reserved for the most unstable, treatment-resistant patients.
Deep transcranial magnetic stimulation
A Taiwanese meta-analysis has helped clarify the role of deep transcranial magnetic stimulation (dTMS) for treatment-resistant depression. The meta-analysis included 198 patients with treatment-resistant depression who underwent dTMS and 219 who received sham treatment in a total of 15 studies, only three of which were randomized controlled trials.
Active treatment was associated with a 2.06-fold increased likelihood of remission of depressive symptoms; however, the effect was statistically significant only in the subgroup of patients on concurrent antidepressant medication. Moreover, the therapeutic benefit of dTMS was significantly greater in the nonrandomized studies, where the odds ratio for remission was 3.8-fold greater than with sham therapy. In contrast, the odds ratio for remission with dTMS dropped to 1.37 in the randomized trials (Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109850. doi: 10.1016/j.pnpbp.2019.109850). “dTMS has quite a bit of antidepressant potential in treatment-resistant depression, but as an augmentation strategy. More randomized trials are needed, with a particular focus on which classes of antidepressants might be most effective as concurrent therapy,” Dr. Sartorius concluded.
He reported having no financial conflicts regarding his presentation.
SOURCE: Sartorius A. ECNP 2020, Session TP.03.