Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol

Background: About 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. Methods: Patients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-& Aring;sberg Depression Rating Scale to analyze the severity of depressive symptoms. Discussion: This clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method.