RecruitingNot ApplicableNCT06937476

Neurobiological Mechanisms of Pathological Rumination and Effects of Aripiprazole

Investigation of the Neurobiological Mechanisms Underlying Pathological Rumination and the Pharmacological Effects of Aripiprazole

Sponsor

Central South University

Enrollment

108 participants

Start Date

May 8, 2025

Study Type

INTERVENTIONAL

Conditions

Major Depressive Disorder (MDD)Rumination

Summary

This randomized, single-blind (assessor-blind) controlled trial aims to investigate the efficacy of aripiprazole as an augmentation strategy for treating pathological rumination in patients with major depressive disorder (MDD). Pathological rumination-defined as repetitive, intrusive, and uncontrollable negative thinking-has been identified as a major transdiagnostic risk factor for the development, maintenance, and recurrence of depression. Even during clinical remission, ruminative symptoms often persist and strongly predict relapse. Previous clinical observations and experimental studies suggest that aripiprazole, a partial dopamine D2 receptor agonist, can significantly improve cognitive symptoms and reduce rumination in MDD patients when added to selective serotonin reuptake inhibitors (SSRIs). However, rigorous randomized controlled trials (RCTs) directly targeting rumination and validating this effect remain limited. In this study, patients with acute MDD episodes and high levels of rumination will be randomly assigned to receive either escitalopram monotherapy (20 mg/day) or escitalopram (20 mg/day) plus low-dose aripiprazole (2.5-5 mg/day) for 8 weeks. The assignment will remain blinded to outcome assessors and data analysts, while patients and treating clinicians will remain unblinded due to dose titration and safety monitoring requirements. Participants will undergo \[18F\]fallypride-PET-MRI scanning at baseline and post-treatment to measure striatal dopamine D2 receptor binding and explore its association with changes in rumination symptoms and treatment efficacy. The primary outcome is the change in Ruminative Responses Scale (RRS) scores. Secondary outcomes include changes in depressive symptoms and dopamine D2 receptor availability. This trial will provide neurobiological insights into the dopaminergic mechanisms underlying pathological rumination and explore the therapeutic potential of D2 receptor modulation in this cognitive domain.

Eligibility

Min Age: 18 YearsMax Age: 45 Years

Plain Language Summary

Simplified for easier understanding

This study is investigating the brain mechanisms behind a type of repetitive, stuck negative thinking called pathological rumination in people with major depression. Researchers are also exploring whether a medication called aripiprazole (commonly used for depression and other mental health conditions) can help reduce this kind of thinking. Brain imaging (MRI and PET scans) will be used. **You may be eligible if...** - You are between 18 and 45 years old - You have been diagnosed with major depressive disorder based on a clinical interview - You are currently in a depressive episode with a significant score on a standard depression scale - You have not taken psychiatric medications (except for sleep aids) in the past 6 weeks - You are right-handed and of Han Chinese ethnicity (as specified in this study) **You may NOT be eligible if...** - You have another psychiatric diagnosis besides anxiety disorders alongside depression - You have depression with psychotic features - You have severe suicidal thoughts or behaviors - You have a history of brain injury or serious medical conditions - You have a pacemaker or metal implants incompatible with MRI/PET scanning Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

DRUGEscitalopram

Escitalopram will be administered orally at a fixed dose of 20 mg/day for 8 weeks. This SSRI antidepressant is used as baseline pharmacological treatment for patients with major depressive disorder (MDD), either as monotherapy or in combination with aripiprazole. No other psychotropic medications are allowed during the study period.

DRUGAripiprazole 5mg

Aripiprazole will be administered as an adjunctive treatment to escitalopram at an initial dose of 2.5 mg/day, titrated up to 5 mg/day based on tolerability. Treatment will last 8 weeks, after which aripiprazole will be tapered and discontinued. This intervention aims to evaluate the efficacy of dopaminergic augmentation in reducing pathological rumination symptoms.