Combining brain stimulation and therapy for treating depression

Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes

This study is testing whether combining brain stimulation with therapy can help adults with major depression feel better by personalizing the treatment to their brain's needs.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT03289923 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of combining MRI-guided repetitive transcranial magnetic stimulation (rTMS) with cognitive behavioral therapy (CBT) in adults suffering from major depressive disorder. Participants will undergo brain MRI scans to identify optimal stimulation sites, followed by a series of rTMS sessions paired with cognitive therapy. The goal is to enhance the efficacy of rTMS by personalizing treatment based on individual neurocircuitry and engaging the brain's emotional regulation circuits during therapy. The study aims to explore how this multimodal approach can lead to significant improvements in depressive symptoms.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 who have a diagnosis of major depressive disorder and have not responded adequately to previous antidepressant treatments.

Not a fit: Patients who do not have major depressive disorder or those who have not previously tried antidepressant medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for individuals with major depressive disorder, potentially leading to better outcomes than current standard therapies.

How similar studies have performed: While rTMS has been used in depression treatment, this specific combination of MRI-guided stimulation and cognitive therapy is a novel approach that has not been extensively tested in previous studies.

Eligibility criteria

* INCLUSION CRITERIA:

  1. 18 to 75 years of age.
  2. Use of effective method of birth control for women able to become pregnant
  3. English speaker
  4. Major Depressive Episode Diagnosis, and Severity:

     1. Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major Depressive Disorder by DSM-IV-TR criteria
     2. HAM-D score \> 17 and Item 1 score greater than or equal to 2. Alternatively: At the initial screening and beginning of Phase II, subjects must have a baseline score on the MADRS \>= 20 and YMRS of \< 12.
  5. Current or past history of lack of response to at least one adequate antidepressant trial, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT would count as an adequate antidepressant trial (unless the ECT occurred within the last year, in which case the participant will be excluded).
  6. If currently on a stable dose of antidepressant medication, the dosage has been unchanged for at least four weeks prior to study entry. The medication must be continued, and at the same dosage throughout study participation.
  7. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
  8. All subjects must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers .
  9. Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.

EXCLUSION CRITERIA:

1. Pregnant or nursing women or women who plan to become pregnant in the next 20 weeks while in the study.

   Persons who are able to get pregnant must be willing to use at least one form of effective birth control during the entire period of study participation (or until last clinical labs and rating) and have a negative pregnancy test at screening.
2. Current or recent (within the past 6 months) diagnosis of substance abuse or dependence (excluding nicotine and caffeine)
3. Past or current history of tinnitus
4. Non English speaker
5. Unable to understand or complete study tasks and instructions
6. History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, participants with history of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on their brain scan, or with loss of consciousness \>5 min, or with other sequelae, excluding headache, lasting \> 24 hours will not be included in the study.
7. Diagnosed with the following conditions (current unless otherwise stated):

   1. Any other current primary Axis I mood or psychotic disorder, including bipolar disorder, with the exception of most anxiety disorders (including generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), specific phobia, panic disorder with and without agoraphobia, posttraumatic stress disorder (PTSD), anxiety secondary to medical condition, acute stress disorder (ASD)), although with obsessive-compulsive disorder (OCD) and substance-induced anxiety disorder excluded. While these anxiety disorders can be comorbid, they must be stable and the MDD must be the primary diagnosis.
   2. Depression secondary to a general medical condition, or substance-induced.
   3. Any bipolar disorder or psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in this or previous episodes.
   4. Eating disorder (current or within the past year).
   5. Obsessive compulsive disorder (lifetime).
   6. Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR criteria, which in the judgment of the Investigator may hinder the subjects in completing the procedures required by the study protocol.
8. Subjects currently engaged or planning to engage in other treatment during the course of Phases I and II of the study (including behavior therapy, or other types of individual, family, or group psychotherapy/counseling), or subjects planning to start an antidepressant medication during the course of Phases I and II.
9. Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that, in the opinion of the investigator, significantly lowers the seizure threshold.
10. Subjects with an unstable or serious medical or neurological disorder.
11. Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) unless if controlled by medications.
12. Presence of any implants, prosthesis, or other permanent alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data.
13. Subjects who have hearing loss that has been clinically evaluated and diagnosed
14. Participants who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 90 minutes, and would feel uncomfortable in the MRI machine (for subjects doing imaging component of the study only).
15. Subjects with any of the following treatment histories:

    1. Lifetime history of TMS treatment.
    2. Lifetime history of treatment with Deep Brain Stimulation or Vagus Nerve Stimulation.
    3. Use of any investigational drug or device within 4 weeks of starting the study.
16. Clinically significant abnormal lab tests
17. Positive HIV test
18. Subjects who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
19. A current NIMH employee/staff or their immediate family member.
20. A positive test for COVID-19 or symptoms consistent with COVID-19 infection
21. Subjects who have allergies to lidocaine or previous adverse reaction to lidocaine.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Carlos A Zarate, M.D. — National Institute of Mental Health (NIMH)
• Study coordinator: Ekaete C Ekpo

Conditions Major Depressive Disorder; Transcranial Magnetic Stimulation; Cognitive Therapy