This pilot study aims to compare two different treatment targets for transcranial magnetic stimulation, an FDA-approved treatment for major depressive disorder (MDD), in terms of their relative efficacy for depression versus anxiety.

Transcranial magnetic stimulation (TMS) is a safe, noninvasive FDA-cleared technique that is commonly used as a treatment for MDD. It has been shown to focally activate specific brain regions that are believed to be underactive in these patients. This study aims to compare two different TMS targets in the prefrontal cortex. TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.

This will be a prospective double-blind randomized controlled trial to assess the comparative efficacy of two different TMS targets within the prefrontal cortex (PFC). The "dysphoric" target in the dorsolateral PFC is believed to be more effective for depression, while the "anxiosomatic" target in the dorsomedial PFC is believed to be more effective for anxiety.

Patients with comorbid depression and anxiety will receive 6 weeks of TMS following standard clinical parameters (30 treatments over 6 weeks, 10 Hz frequency, 3000 pulses) with MRI-guided neuronavigation. Participants will be randomized to either the dysphoric or anxiosomatic target. Both targets are believed to be effective treatments for this patient population. Participants and raters will remain blinded to the group assignment. All participants will receive resting-state functional MRI scans before and after the course of treatment in order to study physiological changes.

The dysphoric target is expected to induce greater relative improvement in depression, while the anxiosomatic target is expected to induce greater relative improvement in anxiety.

Inclusion Criteria:

• Adults age 18 to 65
• Meeting FDA guidelines for clinical TMS (DSM-5 diagnosis of major depressive disorder with at least one failed antidepressant trial)1
• Beck Depression Inventory (BDI) score of 20 or higher
• Beck Anxiety Inventory (BAI) score of 16 or higher

Exclusion Criteria:

• History of:

  • Moderate or severe substance use disorder in the past six months as defined by DSM-5 criteria, with the exception of cannabis and nicotine use disorders.
  • Dementia, as defined by treating neurologist
  • Moderate or severe autism spectrum disorder
  • Bipolar disorder
  • Schizophrenia spectrum disorders

• Current evidence of:

  • Substance-induced mood disorder
  • Active psychotic symptoms
  • Active suicidal ideation

• Contraindications to rTMS treatment:

  • Seizure disorder
  • Significantly elevated seizure risk, as determined by clinician assessment
  • Presence of metallic objects within the head
  • Presence of an implanted neurostimulation device within the head

• Contraindications to MRI

  • Severe claustrophobia
  • Severe pain/illness exacerbated by lying prone in the scanner
  • Presence of non-MRI compatible metal foreign bodies or implants
  • Weight in excess of 350 lbs
  • Shoulder width in excess of maximum tolerable width for scanner

De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.

Participants will be blinded to which target is expected to improve which symptom.

Study investigators (with the exception of the treatment administrator), including the outcomes assessor, will be blinded to which participant is receiving which treatment.