Improving depression treatment using brain stimulation and medication

Neurocomputational Mechanisms of Mood Improvement

This study is testing whether combining brain stimulation with different medications can help adults with major depression feel better by looking at how their brains respond to rewards.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT04276259 on ClinicalTrials.gov

What this trial studies

This study aims to explore how reward learning signals affect responses to antidepressants in adults with major depressive disorder. It involves a 3x3 factorial double-blind design where 120 participants will be randomized into three groups receiving either buprenorphine, naltrexone, or a placebo. Each participant will undergo three sessions of transcranial magnetic stimulation (TMS) targeting the ventromedial prefrontal cortex to manipulate brain activity related to reward learning. The goal is to better understand the mechanisms of antidepressant responses and identify new treatment targets for depression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-55 with major depressive disorder who are currently unmedicated and have had limited previous antidepressant treatment.

Not a fit: Patients who are pregnant or have a history of severe psychiatric disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective treatments for major depressive disorder by targeting specific brain mechanisms.

How similar studies have performed: Other studies have shown promise in using brain stimulation techniques for depression, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

* • Adults, age 18-55 years; fluent in English and with the capacity to understand the nature of the study and sign the written informed consent since the research instruments used in this study are not available in other languages;

  * Written informed consent obtained;
  * A score on the Mood and Anxiety Symptom Questionnaire- Anhedonic Depression (MASQ-AD) ≥ 23 (2/3 sample) and MASQ-AD \< 23 (1/3 sample) with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia);
  * No more than one failed antidepressant trial of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ);
  * Participants can have previous history of antidepressant treatment but will need to be antidepressant medication-free for at least 21 days prior to the collection of imaging data (five weeks for fluoxetine).

Exclusion Criteria:

* • Pregnant or breastfeeding or plan to become pregnant over the duration of the study;

  * History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders;
  * Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for nicotine, or substance abuse in the last 2 months;
  * Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy \< 6 months after study entry);
  * Having epilepsy or other conditions requiring an anticonvulsant;
  * Receiving vagus nerve stimulation, electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation during the current episode.
  * Currently taking any psychiatric medication or other potential augmenting agents (e.g., T3 in the absence of thyroid disease, lithium, buspirone); Taking thyroid medication for hypothyroidism may be included only if they have been stable on the thyroid medication for 3 months;
  * Receiving therapy that is depression specific, such as Cognitive Behavioral Therapy or Interpersonal Psychotherapy of Depression (participants can participate if they are receiving psychotherapy that is not targeting the symptoms of depression, such as supportive therapy, marital therapy);
  * Currently actively suicidal or considered a high suicide risk;
  * Patients are receiving opioid analgesics.
  * Patients are currently dependent on opioids.
  * Patients are in acute opioid withdrawal.
  * Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids.
  * Any individual with a history of sensitivity to buprenorphine or naltrexone.
  * Currently enrolled in another study, and participation in that study contraindicates participation in this study;
  * Any reason not listed herein yet, determined by the site PI and research staff that makes participation in the study hazardous.
  * Having any contraindication for the performance of TMS, such as the presence of a neurologic disorder or medication therapy known to alter seizure threshold (e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches), recurrent seizures or epilepsy in participant or family history of hereditary epilepsy, pregnancy, metallic implants in body or other devices that may be affected by magnetic field or significant heart disease or cerebrovascular disease.
  * Having any contraindication for the performance of an MRI, such as the presence of metal implants or foreign metallic objects (e.g., braces or extensive dental work), severe claustrophobia, or inability to tolerate the scanning procedures.

Where this trial is running

Pittsburgh, Pennsylvania

• Bellefield Tower — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Marta Peciña, MD, PhD — University of Pittsburgh
• Study coordinator: Eli Strohecker, BS

Conditions Major Depressive Disorder; Depression