Modulating Spinal Interoceptive Pathways to Evaluate Their Role and Therapeutic Potential in MDD Symptomatic Domains

Inclusion criteria

• 18 to 60 yrs., inclusive,
• Female or Male,
• With current MDD episode according to MINI 7.0.2. duration (≥4 weeks and

≤ 2 yrs.),

• Current BMI ≥18.5 and ≤ 35.99 kg/mts2
• MADRS score at screening ≥18
• Currently on an FDA- approved antidepressant medication at a stable therapeutic dose for ≥ 8 weeks,
• Psychotherapeutic interventions are allowed if dose/frequency stable for ≥4 weeks,
• Anxiety disorders allowed if no more than moderate in severity and are not the main diagnosis,
• Using an effective contraceptive method (participants with childbearing potential), and 10)Able to complete study related tasks.

Exclusion criteria

• Treatment resistance during current depressive episode (>2 treatment trials at adequate doses/duration), including medication and neuromodulation treatments.
• Current/lifetime diagnosis of bipolar disorder or schizophrenia spectrum disorders.
• Significant risk of suicide according to CSSRS or clinical judgment, or suicidal behavior in the past year.
• Psychotic symptoms during the current MDD episode or in the past 6 months.
• Current (past month) substance use disorder (nicotine, caffeine allowed).
• Current unstable neurological conditions including seizure disorders (infantile seizures are not exclusionary), neurodegenerative disorders, or stroke.
• Evidence of severe peripheral neuropathy.
• History of moderate to severe traumatic brain injury (e.g., skull fracture or loss of consciousness >10 minutes) or spinal cord injury.
• Unstable clinically significant medical conditions (e.g., uncontrolled hypertension as indicated by a systolic >150 mmHg or diastolic >95mmHg).
• History of cancer allowed if remitted for the past 5 years.
• Use of anticonvulsant medications and calcium channel blockers at screening.
• Current severe pain conditions or need for chronic use of pain medication including NSAIDs and opiates.
• Implanted electronic medical devices.
• Neuromodulation interventions in the past month.
• Active skin lesions on electrode placement sites.
• pregnant or breastfeeding.
• Suspected IQ <80.
• Any other relevant clinical reason as judged by the clinician.