N/A
N=24
A Pilot fMRI Study of TMS in Late-Life Severe Worry
Anxiety Disorders Generalized
Bottom Line
View on ClinicalTrials.gov: NCT03577106 ↗Enrolled (actual)
24
Serious AEs
4.2%
Results posted
Jun 2023
Primary outcome: Primary: Change in Worry Severity From Baseline to Post-intervention as Measured by the Penn State Worry Questionnaire (PSWQ) — 62.43; 6.19 units on a scale (PSWQ) — p=<0.005
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Transcranial magnetic stimulation (TMS) (Device)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Carmen Andreescu
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Worry Severity From Baseline to Post-intervention as Measured by the Penn State Worry Questionnaire (PSWQ) |
62.43; 6.19 | <0.005 sig |
| PRIMARY Participants Who Responded to TMS |
2; 19 | — |
Summary
Investigators will test a novel intervention through experimental therapeutic approach using fMRI-directed Intermittent Theta Burst Stimulation (iTBS), a high frequency TMS paradigm, for the treatment of severe, uncontrollable worry. While worry is a universal human experience, severe and excessive worry has been recently linked to increased risk of stroke and other cardiovascular diseases, increased risk of conversion to Alzheimer's disease as well as to higher risk of all-cause mortality in midlife and late-life. Severe, uncontrollable worry has been repeatedly associated with reduced quality of life and impaired functioning. Current treatment choices (antidepressant/anxiolytic medications and psychotherapeutic interventions) have been proven moderately efficacious in reducing anxiety/depression burden, but ineffective in reducing worry severity, a phenomenon that may contribute to the high relapse rates associated with mood and anxiety disorders. Our research indicated that worry severity is associated with hyperactivation in specific regions such as orbital frontal cortex, superior parietal gyrus, amygdala and parahippocampal gyrus. This pilot study will explore the efficacy of targeting one of these regions with iTBS. Based on investigators' previous results, the most accessible target is the right superior parietal gyrus (rSPG) - a region that remained significantly associated with severe worry after controlling for effects of comorbid depression or overall anxiety. As this region showed an increased in cerebrovascular flow in association with worry severity, investigators will use iTBS (5x/week for 2 weeks) to modulate cortical plasticity in this region and consequently, to reduce worry severity.
TMS during wakefulness has been shown to alter subsequent sleep [4], Further, changes in sleep in response to TMS has been associated with how participants respond to the TMS as a treatment [5]. Thus, the study will measure sleep throughout the protocol to determine whether sleep changes as a function of TMS and whether sleep changes are associated with treatment response.
Eligibility Criteria
Inclusion Criteria
- Participants must have completed Dr. Andreescu's study R01MH108509/PRO15080120.
- Penn State Worry Questionnaire score of 55 or above.
Exclusion Criteria
- Any form of psychosis or Bipolar Disorder, dementia, a history of substance abuse within the last six months
- Use of antidepressants within the last five to fourteen days (adequate washout interval to be determined by the principal investigator (PI) based on each specific antidepressant). For fluoxetine, the washout interval will be six weeks. However, for participants who are prescribed low dose psychotropics for pain, sleep disturbances, and/or medical conditions (e.g. amitriptyline for peripheral neuropathy, low dose trazodone as a sleep aid), these will be allowed in most circumstances. We will include participants on certain dosages of the most commonly prescribed antidepressants (for medical reasons) as follows: amitriptyline up to 50 mg/d, doxepin up to 50 mg/d, trazodone up to 100 mg/d, and imipramine up to 50 mg/d. We will review other cases individually and the PI will decide if the participants are eligible for the study and if they may continue the current medication.
- Unable to complete MRI scans: presence of ferromagnetic metal in the body, claustrophobia
- Contraindications for TMS:
- Presence of a neurologic disorder or medical condition known to alter seizure threshold(e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches)
- Recurrent seizures or epilepsy in participant
- Pregnancy
- Metallic implants in body located at 30 cm or less from the position of the magnetic coil; presence in the body of other devices that may be affected by magnetic field (e.g. pacemakers).
- Unable to temporarily discontinue benzodiazepines 48 hours prior to MRI scan. Participants on high doses of benzodiazepines (e.g., greater than or equivalent to 2 mg of lorazepam) will be excluded, given the complexity and potential complications of benzodiazepine taper/withdrawal.
Data sourced from ClinicalTrials.gov (NCT03577106). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.