We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder). 80 participants with an anxiety-related disorder (defined below) will receive 50 active or sham TMS treatments over 5 days (following the SAINT protocol, which is FDA-cleared for MDD. The primary outcome will be the BAI, with a modified recall window to reflect the short treatment interval. Participants randomized to sham will be offered an open-label crossover extension.

We recently derived a novel TMS target for anxiety via lesion and brain stimulation mapping methods. We prospectively tested this target in a sample of participants with major depressive disorder (MDD) with comorbid anxiety symptoms and found that it was more effective for anxiety (median change 60.0% vs 39.8%, p=0.01) than the conventional TMS target for MDD with comorbid anxiety. While these results are promising, it remains unclear how our target works for anxiety-related disorders as opposed to MDD comorbid anxiety symptoms. Furthermore, we used conventional 10 Hz TMS, but accelerated intermittent theta burst stimulation (aiTBS) has now been shown to improve outcomes and is now an FDA approved treatment protocol. Finally, we tested the translational hypothesis that stimulating different circuits can modify different behaviors; clinical efficacy was a secondary outcome.

This double-blinded, randomized, sham-controlled aiTBS trial will test the efficacy of our novel anxiety target. 80 participants with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder) will receive 50 active or sham TMS treatments over 5 days. Changes in anxiety symptoms/processes will be assessed via validated measures (primary outcome measure: Beck Anxiety Inventory) during treatment and follow-up visits up to one-year post-treatment. Participants randomized to sham who do not respond will be offered an open-label crossover extension.

Inclusion Criteria:

• English proficiency sufficient for informed consent, questionnaires/tasks, and treatment

• Diagnosis of one of the following anxiety-related disorders per Quick-SCID:

  • Generalized Anxiety Disorder
  • Social Anxiety Disorder
  • Panic Disorder
  • Posttraumatic Stress Disorder
  • Obsessive Compulsive Disorder

• Moderate level of anxiety (BAI >16)

• One failed psychological or pharmacological treatment

• Stable psychiatric medication regimen for 4 weeks prior to treatment and throughout treatment

• Primary clinician (e.g. psychiatrist, psychologist, therapist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial

• Agreement to abstaining from becoming pregnant from screening to two weeks after treatment (the MRI visit)

Exclusion Criteria:

• • Active pregnancy as determined by a urine pregnancy test

  • Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)

  • History of:

    • Exposure to TMS within the last 3 months
    • Neurosurgical intervention for psychiatric disorders
    • Autism spectrum disorder, intellectual disability, or cognitive impairment that impairs capacity to consent
    • Significant neurological illness deemed to increase risk from treatment
    • Moderate to severe neurodegenerative disease
    • Untreated or insufficiently treated endocrine disorder
    • Treatment with investigational drug or intervention during the study period
    • Bipolar I disorder or schizophrenia

  • Anyone presenting with:

    • Mania or hypomania
    • Psychosis
    • Active suicidal ideation with intent and a plan (defined by Columbia Suicide Severity Rating Scale)
    • Contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia > 4 hours per night with hypnotic, etc.).
    • Current moderate or severe substance use disorder (excluding cannabis or nicotine) or demonstrating signs of acute substance withdrawal

  • Positive urine drug screen for illicit substances for cocaine, amphetamines, phencyclidine, and opioids, except for prescribed medications or known medications with history of resulting in a false positive

  • Existing tinnitus (ringing in the ears)

  • Any other condition deemed by the PI to interfere with the study or increase risk to the participant