Electroconvulsive therapy (ECT) is a well-established treatment for major depressive disorder and has long been considered to be the gold standard for the treatment of patients with treatment-resistant depression (TRD). More recently, repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for the treatment of depressive symptoms, including TRD, and is increasingly being used as a treatment of TRD since its approval by the Food and Drug Administration (FDA) in 2008.
While ECT involves the application of a diffuse electric current in order to induce a generalized seizure in an anesthetized patient, rTMS involves the generation of electromagnetic fields that are applied to the surface of the skull to induce a focal electrical current in brain tissue without the need for anesthesia or the induction of seizures (Camprodon et al, 2016). Atlhough ECT may be more effective acutely, TMS is a less invasive and better tolerated treatment, and therefore has greater acceptability. In addition, recent studies indicate that the antidepressant effects of rTMS are more durable (Camprodon, 2016).
Previous neuroimaging studies have consistently reported volumetric changes in gray matter (GM) in specific brain regions after treatment with ECT. Fewer studies have used neuroimaging to examine structural changes associated with rTMS and have yielded less consistent findings. A recent study from Marta Cano, PhD, Joan Camprodon, MD, MPH, PhD and colleagues in the Laboratory for Neuropsychiatry and Neuromodulation compares brain volumetric changes observed after treatment with right unilateral ECT versus 10 Hz rTMS to the left dorsolateral prefrontal cortex (left DLPFC) in a group of patients with TRD. This is the first neuroimaging study in the literature that directly compares the brain volumetric correlates of ECT and rTMS.
Similar Clinical Outcomes for ECT and rTMS
In this prospective observational study, participants with treatment-resistant depression received either right unilateral ECT (n=15) versus 10 Hz rTMS to the left DLPFC (n=17). Major depressive disorder was confirmed using the Mini-International Neuropsychiatric Interview 6.0 (MINI). Structural magnetic resonance imaging (MRI) was conducted at baseline (within 10 days of the initiation of treatment) and after treatment (within 10 days of the last treatment session).
Both groups experienced a reduction in the severity of depressive symptoms measured using the Quick Inventory of Depressive Symptoms (QIDS). Fifteen patients with TRD received a course of RUL ECT. The number of treatments ranged from 6 to 21 (mean = 12.07). The mean QIDS score prior to ECT initiation was 18 ± 3.38 and the mean QIDS score after ECT was 12 ± 5.21.
Seventeen patients with TRD received a left DLPFC rTMS. The first 30 treatments were applied 5 days per week (Monday-Friday) for 6 weeks and the last 6 treatments were delivered over the course of 2 to 3 weeks. The mean QIDS score prior to rTMS initiation was 15.06 ± 2.84, and the mean QIDS after the completion of rTMS was 9.35 ± 5.78.
Volumetric Changes: ECT versus rTMS
Patients who received RUL ECT, compared to those treated with rTMS, showed greater gray matter volumetric changes, with increases observed in the right hemisphere in the striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. In contrast, No significant gray matter volume changes were observed in patients treated with rTMS.
These findings indicate that despite comparable clinical outcomes, RUL ECT, but not rTMS, is associated with structural changes in specific regions of the brain. In addition, this study demonstrated that ECT- or rTMS-induced brain volumetric changes were not correlated with degree of clinical improvement. In other words, clinical improvement was observed in the absence of structural volumetric changes.
Understanding How ECT and rTMS Work to Treat Depression
Recent research suggests that ECT-induced volumetric changes could result from structural neuroplastic changes, such as neurogenesis, synaptogenesis, gliogenesis and angiogenesis. Other studies have suggested that ECT-induced structural changes might depend on neuroinflammatory mechanisms (by increasing the permeability of the blood-brain barrier and increasing fluid volume and/or activating immune cellular responses).
Although the current study does not indicate that rTMS stimulates macroscopic structural changes, we cannot rule out neuroplastic changes occurring at other levels of brain organization, specifically neurophysiological plasticity at the cellular, synaptic or circuit-based levels. For example, a previous study from Barbour and colleagues (2019) demonstrated that in patients with TRD deficits in connectivity observed using functional MRI normalized after treatment with DLPFC rTMS. Thus, rTMS appears to selectively modulate dysfunctional network dynamics without evident structural reorganization.
In conclusion, these findings suggest that RUL ECT and rTMS to the left DLPFC have similar clinical antidepressant properties but different brain volumetric correlates. While structural neuroplasticity and/or neuroinflammation may be induced by ECT, TMS does not seem to induce macroscopic structural changes. However, previous studies suggest that both ECT and TMS induce neurophysiological plasticity at the circuit level. More broadly, the findings of this study support the notion that there are different mechanistic circuit-level therapeutic strategies with antidepressant efficacy.
Other contributors to this research include Erik Lee, Christopher Polanco, Tracy Barbour, Kristen Ellard, Blake Andreou, Sofia Uribe, Michael Henry, Stephen Seiner, Narcís Cardoner, and Carles Soriano-Mas.
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Barbour T, Ellard K, Camprodon J. Individualized TMS target selection for MDD: clinical outcomes, mechanisms of action and predictors of response. Brain Stimul. 2019; 12(2): 516.
Camprodon JA. Are we ready for TMS maintenance? Psychiatric News, 2016.
Camprodon JA, et al. Psychiatric Neurotherapeutics: Contemporary Surgical and Device-Based Treatments (Current Clinical Psychiatry), 1st Edition, 2016.
Cano M, Lee E, Polanco C, Barbour T, Ellard KK, Andreou B, Uribe S, Henry ME, Seiner S, Cardoner N, Soriano-Mas C, Camprodon JA. Brain volumetric correlates of electroconvulsive therapy versus transcranial magnetic stimulation for treatment-resistant depression. J Affect Disord. 2023 Jul 15; 333: 140-146.
Marta Cano, PhD is currently a postdoctoral researcher at Sant Pau Biomedical Research Institute, where she is leading the Neuroimaging & Affective Disorders Lab of the Sant Pau Mental Health Research Group, and a research fellow of the Laboratory for Neuropsychiatry & Neuromodulation at Mass General. Her research interests are primarily focused on understanding the dimensional impact of rapid-acting antidepressants on patients with treatment-resistant depression with the final aim to develop a personalized prediction model of antidepressant treatment response.
Joan A. Camprodon, MD, MPH, PhD is the Chief of the Division of Neuropsychiatry, Director of the Transcranial Magnetic Stimulation (TMS) Clinical Service, Director of the Laboratory for Neuropsychiatry & Neuromodulation at Mass General, and an Associate Professor of Psychiatry at Harvard Medical School. His research uses multimodal combinations of brain stimulation, neuroimaging, and neurophysiology to investigate neural circuitry and plasticity in a translational manner. His research includes basic, translational, and clinical projects focused on human circuit neuroscience. Critical efforts are geared towards applying the paradigms and methods of human systems/cognitive neuroscience to discover treatment targets that support the development of individualized precision therapeutics, with a focus on image-guided device-based neuromodulation.
