Á. Moleón-Ruiz et al. present Enhanced Bilateral Accelerated Theta Burst Stimulation for Comorbid Anxiety and Depressive Disorders: The Seville Protocol, published in Alpha Psychiatry (AP), Volume 26, Issue 6 (https://www.imrpress.com/journal/AP/26/6/10.31083/AP45254).

Dr. Manuela Martín-Bejarano

We are honored to invite Dr. Manuela Martín-Bejarano to interpret the article. Dr. Manuela Martín-Bejarano is a Clinical Neuropsychologist and Neuroscience Researcher with a PhD in Health Sciences and Biomedicine from the University of Cádiz. She is currently a Research Coordinator at the Andalusian Institute for Brain Health, where she works in the Neuromodulation Unit.

Her research focuses on neurocognition, psychiatric disorders, and non-invasive neuromodulation techniques, particularly transcranial magnetic stimulation. She has participated in national and international research projects funded by institutions such as Horizon 2020 and the Instituto de Salud Carlos III, and has published in peer-reviewed international journals. She combines clinical practice, research, and academic teaching, with experience in both hospital and university settings.

 

Author's Interpretation

In daily clinical practice, treating TRD with comorbid anxiety is especially challenging, and although TMS is effective, standard protocols can be difficult to implement due to the need for daily 30- to 40-minute sessions over four to six weeks.

This clinical reality led us to evaluate a more intensive and time-efficient approach.

Based on this idea, we developed what we call the Seville Protocol, an accelerated bilateral TBS approach targeting the dorsolateral prefrontal cortex—enhancing excitability on the left and reducing it on the right—to address both depressive and anxiety symptoms.

We used high stimulation intensities, delivered 1,800 pulses per target, and scheduled a total of 30 sessions over just three weeks, using MRI-guided neuronavigation.

We then carried out a retrospective naturalistic study including 64 patients with TRD and clinically significant anxiety. Depressive and anxiety symptoms were assessed using the Hamilton Rating Scales before and after treatment.

We observed meaningful improvements in both symptom domains. Almost half of the patients showed a clinical response in depressive symptoms, with about one third reaching remission. Anxiety symptoms also improved, with response rates close to 50 percent and remission rates around 25 percent. The protocol was well tolerated, with no serious adverse events.

When we explored predictors of outcome, a family history of mental disorders appeared to be associated with a lower probability of response for depression. However, this association did not remain significant after correction for multiple comparisons.

Although confirmation in randomized controlled trials is still needed, our findings suggest that the Seville Protocol is a feasible, practical, and time-efficient option for TRD with comorbid anxiety.

As a next step, we are currently exploring neuroimaging, genomic, and electrophysiological biomarkers to identify patients most likely to benefit.

(This interpretation reflects the author’s academic perspective and should not be considered clinical guidance.)

 

Original Article:

Enhanced Bilateral Accelerated Theta Burst Stimulation for Comorbid Anxiety and Depressive Disorders: The Seville Protocol: https://www.imrpress.com/journal/AP/26/6/10.31083/AP45254

 

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