Exploring brain activity changes in treatment-resistant depression

The Impact of Working Memory and Reward Markers on DLPFC Activity in Treatment-resistant Depression

This study is testing how a brain stimulation treatment can help people with depression who haven't found relief from other therapies by looking at changes in brain activity and memory.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Unity Health Toronto (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06163625 on ClinicalTrials.gov

What this trial studies

This study investigates how working memory and reward markers influence brain activity in the dorsolateral prefrontal cortex (DLPFC) of individuals with treatment-resistant major depressive disorder (MDD). Participants will undergo repetitive transcranial magnetic stimulation (rTMS), a non-invasive procedure that uses magnetic fields to stimulate specific brain areas, alongside assessments through interviews, questionnaires, brain scans, and saliva samples. The goal is to better understand the mechanisms by which rTMS alleviates depressive symptoms in patients who have not responded to traditional treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a diagnosis of major depressive disorder who have not responded to previous antidepressant treatments.

Not a fit: Patients who do not meet the criteria for major depressive disorder or those who have not failed multiple antidepressant trials may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for individuals suffering from treatment-resistant depression.

How similar studies have performed: Other studies utilizing rTMS have shown promising results in treating depression, suggesting that this approach may be effective.

Eligibility criteria

Inclusion Criteria:

Depressed Participants:

1. Between the ages of 18 and 65 years old.
2. Capable of giving voluntary and informed consent.
3. Fluent in English.
4. Meet Diagnostic and Statistical Manual criteria for single or recurrent Major Depressive Disorder (current major depressive episode), confirmed via the Mini-International Neuropsychiatric Interview (MINI).
5. Moderate to severe depression severity, defined as a 17-item Hamilton Depression Rating Scale260 score ≥ 18.
6. Have failed to achieve a clinical response to an adequate dose of an antidepressant based in an Antidepressant Treatment History Form (ATHF) score ≥ 3 in the current episode, or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (AHTF = 1 or 2)
7. Have had no initiation or dose change in any psychotropic medication in the four weeks prior to screening.
8. If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study.
9. Can adhere to the study schedule.

Nondepressed Participants:

1. Between the ages of 18 and 65 years old.
2. Capable of giving voluntary and informed consent.
3. Fluent in English.
4. No current or previous history of psychiatric diagnoses.
5. Absent/non-clinical depression severity, defined as a 17-item Hamilton Depression Rating Scale260 \< 8.
6. No history of antidepressant use, as measured by the ATHF.

Exclusion Criteria:

All Participants:

1. Are pregnant/lactating.
2. Acute suicidality, defined as a score \>3 on the 17-item Hamilton Depression Rating Scale, Item #3.
3. A MINI-confirmed diagnosis of bipolar disorder, or another comorbidity (e.g., obsessive-compulsive disorder, post-traumatic stress disorder) that is primary in severity and disability relative to their MDD.
4. Other major medical comorbidities requiring immediate investigation or treatment, cardiac pacemaker, or implanted medication pump.
5. Lifetime history of psychosis, including schizophrenia, schizoaffective disorder, delusional disorder, or current psychotic symptoms.
6. Drug abuse or dependence within the last 6 months, excluding caffeine and nicotine.
7. Contraindication to receiving the rTMS (e.g. history of seizure, cochlear implants, benzodiazepine use (lorazepam or equivalent daily dose \>2mg daily), cardiac pacemaker, implanted neurostimulator, significant head trauma with loss of consciousness for greater than or equal to 5 minutes).
8. Electroconvulsive therapy (ECT) within the current depressive episode.
9. Presence of contraindications for MRI, including metallic implants.
10. Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, dementia, significant head trauma with loss of consciousness for greater than or equal to 5 minutes.

Where this trial is running

Toronto, Ontario

• Unity Health Toronto — Toronto, Ontario, Canada (Recruiting)

Conditions Major Depressive Disorder; Treatment Resistant Depression