Imaging- vs. Scalp-Targeted Accelerated TMS for Depression: The Number Needed to Scan Trial

Depression severity rating scale (0-60, higher numbers indicate higher depressive symptom severity). The MADRS is a clinician rated scale consisting of 10 items, with each item scored on a 7 point scale.

For the primary outcome, investigators will assess MADRS as a continuous variable (i.e., MADRS change from baseline to one month after treatment) using a mixed-effects model for repeated measures (MMRM). The model will include group assignment, baseline MADRS score, assessment time point, and time point by treatment interaction as explanatory variables.

Hypothesis: There will be a significant group x time interaction on MADRS score from baseline, immediately post-treatment (Day 5), one-week post-treatment, and one-month post-treatment.

Depression severity rating scale (0-60, higher numbers indicate higher depressive symptom severity). The MADRS is a clinician rated scale consisting of 10 items, with each item scored on a 7 point scale. For the secondary outcomes, investigators will assess MADRS as a categorical variable (i.e., MADRS response defined as ≥ 50% improvement one month after treatment) using a generalized estimating equations approach (GEE).

Hypothesis: One month after treatment, there will be a significantly larger response rate (≥ 50% MADRS improvement) in the imaging- vs. scalp-targeted group using a z-test for proportions. This response rate will be used to calculate an absolute risk reduction and a "number needed to scan" (NNS) with confidence intervals.

The correlation between clinical improvement (i.e., BDI-II) and the distance between the actual (stimulated) scalp-based target and the (predicted but not stimulated) imaging-based target. The BDI-II is a depression severity rating scales (0-63, higher numbers indicate higher severity).

Mediation analyses that includes the mediator variable (i.e., distance) in the multivariable model for the outcome (i.e., MADRS improvement). Investigators will implement a form (i.e., counterfactual-based) causal mediation analysis that estimates the controlled direct and indirect effects and the bias-corrected bootstrap confidence intervals while controlling for confounders such as age, sex, and other related variables (e.g., baseline antidepressant use, etc.).

Hypothesis: In the scalp-targeted aTMS group, clinical improvement will negatively correlate with the distance between the actual (stimulated) scalp-based target and the (predicted but not stimulated) imaging-based target.

Depression severity rating scales (0-63, higher numbers indicate higher severity)

Anxiety severity rating scale (0-63, higher numbers indicate higher severity)

Depression severity rating scales (0-64, higher numbers indicate higher severity)

Anxiety severity rating scale (0-80, higher numbers indicate higher severity)

A single question assessing a patient's perception of their health or condition (scores range from 1-7, one being the participant believes they are not at all ill, seven being an extremely ill individual) and rate their overall change in condition (scores range from 1-7, one being very much improved and seven being very much worse).

A single question asking participants to rate their current mood on a scale of 1-100 (higher scores indicate positive mood)

Transdiagnostic rating scale (each question rated 0-4) Minimum score: 0 Maximum score: 92 Higher score indicates worse outcome or worse overall psychiatric burden

ADHD rating scale (each question rated 1-5, higher scores indicate symptoms highly consistent with ADHD)

13 item scale measuring how illness affects function. Scored 13-91, higher score indicates higher illness intrusiveness severity

10-item questionnaire used to screen for BPD (scores range from 0 to 10; higher scores are associated with higher levels of/more severe BPD symptoms).

Stress assessment scored 0-40, higher scores indicate higher stress

Scale for assessing self compassion (scores range from 1-5, with higher scores indicating greater well-being).

A tool used to assess the potential stress associated with different life events (scores range from 0 to 430, with higher scores indicating higher levels of stress).

24 items with responses ranging from 1 to 5; a higher score would indicate a higher level of spiritual transcendence.

11 item scale evaluating mania. Scored 0-60. Higher score indicates worse outcome/higher mania

26-item questionnaire assessing an individual's perception of their quality of life (scores range from 0 to 100, where higher scores represent a better quality of life).

36-item functional assessment (each question rated 1-5) Minimum: 36 Maximum: 180 Can also be scored by percentiles Higher score indicates more disability

Computer task measuring reaction time

Computer task measuring accuracy and reaction time to emotional faces

Computer task measuring accuracy and reaction time

Computer task measuring accuracy and reaction time to emotional faces

25-item self-report questionnaire used to assess the impact of tinnitus on a person's daily life (scores range from 0 to 100; higher scores indicate a greater tinnitus handicap impact)

16-item self-report questionnaire used to assess the degree to which individuals fear the physical sensations associated with anxiety (scores range from 0 to 64; higher scores indicate greater anxiety sensitivity).

77-item self-administered questionnaire that measures the constructs of effortful control, negative affect, extraversion/surgency, and orienting sensitivity (higher scores indicate presence of listed temperament characteristics).