CARED : A Novel Rapid Treatment Paradigm for Depression

The Carolina Recovery From Depression Protocol (CARED) : A Novel Rapid Treatment Paradigm for Depression

The purpose of this study is to primarily assess the feasibility and secondarily assess the efficacy of a single session intervention (SSI) that combines non-invasive brain stimulation and psychotherapy for Major Depressive Disorder (MDD). investigators will recruit 30 people with MDD, with at least mild to moderate symptoms, who are resistant to typical treatments for Major Depressive Disorder. In this trial, participants will receive psychotherapy, Intermittent Theta Burst Stimulation Transcranial Magnetic Stimulation (iTBS), and either active or sham (placebo) Transcranial Alternating Current Stimulation (tACS).

The purpose of this study is to primarily assess the feasibility and secondarily assess the efficacy of a single session intervention (SSI) that combines non-invasive brain stimulation and psychotherapy for Major Depressive Disorder (MDD). Investigators will recruit 30 people with MDD, with at least mild to moderate symptoms, who are resistant to typical interventions for Major Depressive Disorder. In this trial, participants will receive 3 interventions in a single session: psychotherapy, Intermittent Theta Burst Stimulation (iTBS), and participants will be randomized to receive either active or placebo Transcranial Alternating Current Stimulation (tACS). Additionally, Clinical assessments of depression symptoms are performed at Screening (for eligibility), Baseline (at start of day, prior to any intervention), Follow up 1 (FUP1); 2 weeks after SSI) and Follow up 2 (FUP2; 3 months after SSI). Additional assessments of anxiety symptoms, emotion regulation, clinical improvement and quality of life are included.

Primary Objective:

• Establish the safety, feasibility, and tolerability of the SSI

Second Objective:

• Establish the efficacy of the SSI for the treatment of depression symptoms by determining symptom reduction 2 weeks after completion of SSI.
• Determine whether the combined effect of psychotherapy, TMS and tACS for treating depression reduces symptoms above and beyond TMS and therapy alone at FUP1.
• Determine the longevity of intervention effectiveness (if effective) via follow up (FUP) timepoints for both groups and between groups by comparing scores at FUP1 to scores at FUP2

Inclusion Criteria:

• Any gender, aged 18 - 70
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• DSM-5 diagnosis of unipolar, non-psychotic MDD as evidenced by the Diagnostic Interview for Anxiety, Mood, and Obsessive-Compulsive and Related Neuropsychiatric Disorders (DIAMOND)
• HDRS-17 score ≥14
• Low suicide risk (defined for this study as no active suicidal ideation in the past month and no suicide attempts, preparatory actions, or significant non-suicidal self-harm in the previous 2 years). Risk will be assessed utilizing the Columbia-Suicide Severity Rating Scale (C-SSRS) screen and triage version with further exploration of positive responses.
• Capacity to understand all relevant risks and potential benefits of the study (informed consent).
• For people of childbearing potential: use of highly effective contraception as determined by the Investigator for at least 1 month prior to screening and agreement to use such a method during study participation
• History of treatment resistance as indicated by previously or currently not achieving clinically significant symptom reduction on at least one antidepressant medication. This will be evaluated using the Maudsley Treatment Inventory (MTI). Participants with scores greater than or equal to 3 on the MTI will be included.

Exclusion Criteria:

• DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND
• DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months, as evidenced by the DIAMOND
• Lifetime history of bipolar disorder, as evidenced by DIAMOND
• Schizophrenia spectrum and other psychotic disorders, as evidenced by DIAMOND
• History of autism spectrum disorder (self-reported by participants)
• Initiated any new psychotropic medication in the 6 weeks prior to screening or had a dose change in the preceding 6 weeks
• Initiated a new course of psychotherapy in the 6 weeks preceding screening
• Received any neurostimulation treatment in the 6 weeks preceding screening
• History of seizures (excluding febrile seizures in childhood or Electroconvulsive Therapy (ECT) induced seizures)
• Neurological disorders that would increase risk of participation or present a significant confounder in the opinion of the investigator (for example, dementia, history of stroke, Parkinson's disease, multiple sclerosis, history of traumatic brain injury with prolonged loss of consciousness, ruptured cerebral aneurysm, previous CNS radiation)
• Previously failed to respond to ECT or transcranial magnetic stimulation (TMS)
• Prior brain surgery and/or brain implants
• Personal or familia history of epilepsy
• Previous fainting spells or syncope
• Metal in the brain, skull or elsewhere in the body
• Implanted medical device that uses electricity and any implanted devices in other areas of the head or neck, or implants located < 30cm from the position of the TMS coil
• Current pregnancy or lactation
• Currently enrolled in another clinical trial for depression
• Unstable medical disorder or anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the opinion of the Investigator
• Non-English speaking individuals are excluded because the ability to accurately and completely communicate study information, answer questions about the study, and obtain consent in the English language are necessary, and due to resource constraints it is not feasible to engage an interpreter for language services.