Single-case Intervention Study for Visual Screening Assessment for Proof of Concept and Prediction of Clinical Response to Brexiprazole as Adjunctive Treatment in Adults With Major Depressive Disorder. (ETBREX)

Major Depressive Disorder (MDD) is the most prevalent mental disorder in the world, with high rates of recurrence and dysfunction. A significant portion of patients do not respond adequately to conventional treatments, highlighting the need to search for biomarkers capable of predicting clinical response.

A relevant marker in depression is attentional bias, which is characterized by the preferential processing of negative stimuli, and is inferred as a useful tool in the diagnosis and treatment of depression. The best way to measure attentional bias is through eye-tracking.

In a smaller body of evidence, it is indicated that pharmacological treatment of depression is able to modify the visual tracking pattern, directing it towards a tendency towards normalization when compared to healthy controls, and that this precedes the clinical response.

The study proposes a single-case, blinded design conducted at the Institute of Psychiatry of the HC-FMUSP to evaluate whether visual tracking patterns obtained by eye-tracking in the first weeks of treatment with brexpiprazole (1 and 2 mg/day) as an adjunct in adults with MDD are able to predict clinical response when compared to placebo.

The primary outcome will be measured by the MADRS questionnaire and the secondary outcome by the Clinical Global Impression (CGI). The eye-tracking assessment will use the Tobii eye-tracker 250 Hz device, with images from the International Affective Picture System (IAPS), and will be performed weekly over 10 weeks. It is expected to establish eye-tracking as a low-cost tool to assist in predicting therapeutic response in depression.

Study Overview

• Status: Active, not recruiting
• Conditions: Depression - Major Depressive Disorder
• Intervention / Treatment: Device: Eyetracking (Tobii Pro Fusion 250 hz)

• Study Type: Interventional
• Enrollment (Estimated): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital das Clínicas da faculdade de medicina da Universidade de São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients will be initially assessed through a clinical interview by a specialized psychiatrist and subsequently by a second interviewer who will use the eligibility criteria and screening and diagnostic confirmation instruments below to delineate the sample universe, and must meet the following criteria before randomization:
• Diagnosis of MDD, in a single or recurrent, non-psychotic episode, as defined by the DSM-IV-TR through specialized clinical evaluation and confirmed by the Mini International Neuropsychiatric Interview (MINI - Amorim, 2000);
• The current depressive episode must have a duration of ≥ 8 weeks;
• Inadequate response to ≤ 2 attempts at pharmacological treatment for the current episode of MDD, including the treatment the patient is undergoing at the time of screening, with each attempt lasting a minimum of 4 to 6 weeks, with a first-line antidepressant (SSRI or SNRI) and with a minimum effective dose (defined by the package insert) or higher;
• Inadequate response is defined as: < 50% reduction in the severity of depressive symptoms, as measured by the subject's self-report score on the Visual Analogue Scale (VAS);
• Be between 18 and 60 years of age, inclusive;
• Have a score ≥ 24 on the Montgomery-Åsberg Depression Scale (MADRS);
• Have read and signed the informed consent form (Appendix 1) after the nature of the study has been fully explained and before any study-related procedures are performed;
• Female patients must be:
• Postmenopausal for at least one year, or;
• Surgically unable to conceive (having undergone hysterectomy or bilateral oophorectomy or tubal ligation or otherwise unable to conceive), or;
• Practicing an acceptable method of birth control (defined as: hormonal contraceptives, spermicide plus barrier, a single vasectomized partner and/or intrauterine device);
• If a potentially pregnant patient is practicing an acceptable method of birth control (as mentioned above), she must have a negative urine pregnancy test at enrollment, as well as at baseline, before receiving the study drug.

Exclusion Criteria:

• Potential patients who meet any of the following criteria will be prohibited from participating in the study:
• Known contraindication to brexpiprazole or known hypersensitivity;
• Individuals who report treatment with adjunctive antipsychotic medication to an antidepressant during the current major depressive episode;
• Individuals who have a history of ECT (electroconvulsive therapy) treatment at any time in the past or present, or who have received vagus nerve stimulation or an implanted deep brain stimulation device for the treatment of treatment-resistant depression;
• Individuals currently requiring hospitalization or who have been hospitalized in the four weeks prior to screening for the current major depressive episode;
• Exposure to any other experimental drug or device in the 30 days prior to inclusion, except for previously described antidepressant use;
• Use of benzodiazepines and/or hypnotics (including non-benzodiazepine inducers) within 1 week prior to the start of the study, but excluding short-acting non-benzodiazepine sleep inducers (i.e., zolpidem, zaleplon, zopiclone, and eszopiclone only);
• Pregnancy, breastfeeding, or patients intending to become pregnant during the study;
• Evidence of renal impairment, defined as serum creatinine levels > 133 mmol/L in men, > 124 mmol/L in women, which correspond to > 1.51 mg/dL and > 1.41 mg/dL, respectively, at Week 1 of inclusion;
• Evidence of clinically significant hepatic impairment (defined as AST or ALT > 2 times the upper limit of normal) at Week 1 of inclusion;
• Significant cardiovascular disease, including a history of myocardial infarction in the last 5 years, stroke, clinically significant valvular heart disease, unstable angina, clinically abnormal ECG, arrhythmia, or congestive heart failure, resulting in cardiovascular disability functional class III or IV (NYHA, 1964);
• Uncontrolled hypertension (defined as a diastolic blood pressure ≥ 100 mmHg and/or a systolic blood pressure ≥ 180 mmHg with or without medication).

Hypertensive patients receiving medication must have been receiving the same dose of the same antihypertensive medication for at least two months;

-Evidence of uncontrolled thyroid disorders, including hyper- or hypothyroidism or abnormal TSH levels. Patients known to be on thyroid hormone replacement therapy must have been on a stable dose for at least three months prior to inclusion and have a normal TSH level at inclusion;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brexipirazole Treatment + Eye-Tracking Assessment(Tobii Pro Fusion 250 hz); Participant with depression disorder will undergo baseline eye-tracking (Tobii Pro Fusion 250 hz)assessment followed by treatment with brexipiprazole. Eye-tracking (Tobii Pro Fusion 250 hz) data will be used to evaluate its predictive value for clinical response to pharmacological treatment.	Device: Eyetracking (Tobii Pro Fusion 250 hz); Intervention with brexpiprazole in paciente with depression; Other Names: Brexpiprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between baseline eye-tracking measures and clinical response to naltrexone	Predictive accuracy of baseline eye-tracking metrics for clinical response to naltrexone treatment in individuals with gaming disorder	Baseline to Week 8

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Hermano Tavares, Professor associate

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Actual): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: Depression Brexpiprazole

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No