Depression, Major Depressive Disorder
Conditions
Keywords
Transcranial Magnetic Stimulation, rTMS, F3, 5.5cm rule, Targeting, TMS
Brief summary
The purpose of this study is to examine the effects of different treatment locations using repetitive transcranial magnetic stimulation (rTMS) to treat major depressive disorder.
Detailed description
Currently there is little standardization between rTMS treatment programs as to what is the best way to localize the left dorsolateral prefrontal cortex, which is the FDA-approved treatment location for clinical rTMS for major depressive disorder (MDD). Different targeting methods yield locations that can vary by up to a few centimeters. By comparing different treatment locations and obtaining neurobehavioral, neuroimaging, cognitive, and neuropsychological measures, this study would provide the opportunity to identify the optimal treatment targeting method when using rTMS for major depressive disorder in a clinical setting. This study will specifically be focusing on comparing the two most common targeting methods: a target 5.5cm anterior to the motor strip on the left prefrontal scalp and the F3 target location on the left prefrontal scalp as identified using the 10-20 EEG system nomenclature.
Interventions
DEVICERepetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments.
Sponsors
Nicholas Trapp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of major depressive disorder * Age between 18 and 90 years * rTMS is clinically indicated as determined by clinical rTMS physician team at University of Iowa
Exclusion criteria
* rTMS contraindication such as implanted ferromagnetic material in the head or history of epilepsy with poorly controlled seizures * MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates on General Anxiety Disorder 7-Item Assessment | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Comparison of the response rate (\>50% improvement) for the General Anxiety Disorder 7-Item Assessment between the 2 groups post-treatment. |
| Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Comparison of the response rate (\>50% improvement) and remission rate (score \<5) for the Patient Health Questionnaire 9-Item Assessment between the 2 groups post-treatment. |
| Response and Remission Rates on Montgomery-Asberg Depression Rating Scale | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Comparison of the response rate (\>50% improvement) and remission rate (score \<10) for the MADRS between the 2 groups post-treatment. |
| Percentage Change in Patient Health Questionnaire 9-Item Assessment Score | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Overall change in total Patient Health Questionnaire 9-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assessment measures depression severity at baseline. Total scores of 5, 10, 15, and 20 represent markers for mild, moderate, moderately severe, and severe depression, respectively. All 9 items are summed to compute a total score, ranging from 0-27. Higher scores indicate more severe self-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms. |
| Percentage Change in Montgomery-Asberg Depression Rating Scale Score | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Overall change in total Montgomery-Asberg Depression Rating Scale score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This scale assesses depression severity at baseline. Scores of 8, 17, and 34 are cut-off points for mild, moderate, severe depression, respectively. This 10 item scale is summed to compute a total score, ranging from 0-60. Higher scores indicate more severe clinician-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms. |
| Percentage Change in General Anxiety Disorder 7-Item Assessment Score | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Overall change in total General Anxiety Disorder 7-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assesses anxiety severity as baseline. Scores of 5, 10, and 15 are cut-off points for mild, moderate, and severe anxiety, respectively. All 7 items are summed to compute a total score, ranging from 0-21. Higher scores indicate more severe self-rated anxiety symptoms. Negative change from baseline implies a decrease in anxiety symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Emotion Measures | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | T Score Changes in National Institutes of Health Toolbox Emotional Battery A T score of 50 corresponds to the population mean. Scores may range from 20-80 with a standard deviation of 10. Higher T scores indicate a higher endorsement of each domain. Here, we present changes in mean score from pre-treatment to post-treatment. In that way, a positive value represents a decrease in average T score, and vice versa. |
| Montreal Cognitive Assessment Score Changes | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | Change in Montreal Cognitive Assessment scores from baseline to final timepoint. Reported here as the mean difference in total Montreal Cognitive Assessment score from baseline to endpoint. Montreal Cognitive Assessment is used a screen for cognitive impairment, calculated by adding the points from each task, which range from 0-30. Higher scores indicate little to no cognitive impairment 26 or above: Normal cognition 18-25: Mild cognitive impairment 10-17: Moderate cognitive impairment Fewer than 10: Severe cognitive impairment |
Countries
United States
Participant flow
Pre-assignment details
2 subjects withdrew before randomization 12 subjects were excluded due to head circumference \>60cm 2 refused randomization 2 subjects were not randomized for an unspecified reason
Participants by arm
| Arm | Count |
|---|---|
| 5.5cm Rule Group rTMS will be targeted at a left prefrontal target 5.5cm anterior to the primary motor strip identified on the scalp during motor threshold testing.
Repetitive transcranial magnetic stimulation: Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments. | 47 |
| F3 Group rTMS will be targeted at the left prefrontal scalp target identified as F3 according to the 10-20 EEG system.
Repetitive transcranial magnetic stimulation: Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments. | 58 |
| Total | 105 |
Baseline characteristics
| Characteristic | 5.5cm Rule Group | F3 Group | Total |
|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 15.8 | 44.7 years STANDARD_DEVIATION 15.1 | 43 years STANDARD_DEVIATION 15.45 |
| Comorbidities ADHD | 3 participants | 12 participants | 15 participants |
| Comorbidities Anxiety disorders | 26 participants | 24 participants | 50 participants |
| Comorbidities Borderline Personality Disorder | 7 participants | 5 participants | 12 participants |
| Comorbidities OCD | 2 participants | 4 participants | 6 participants |
| Comorbidities PTSD | 8 participants | 7 participants | 15 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 57 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| General Anxiety Disorder 7-Item Assessment | 14.3 total score STANDARD_DEVIATION 4.7 | 13.5 total score STANDARD_DEVIATION 5.2 | 13.9 total score STANDARD_DEVIATION 5 |
| Montgomery-Asberg Depression Rating Scale | 29.1 total score STANDARD_DEVIATION 6.9 | 29.8 total score STANDARD_DEVIATION 5.9 | 29.5 total score STANDARD_DEVIATION 6.4 |
| Number of Medication Trials | 10.0 medications STANDARD_DEVIATION 5.4 | 9.8 medications STANDARD_DEVIATION 4.9 | 9.9 medications STANDARD_DEVIATION 5.15 |
| Patient Health Questionnaire 9-Item Assessment | 18.8 total score STANDARD_DEVIATION 4.3 | 17.8 total score STANDARD_DEVIATION 4.9 | 18.3 total score STANDARD_DEVIATION 4.6 |
| Psychiatric Medications Antidepressants | 43 Participants | 55 Participants | 98 Participants |
| Psychiatric Medications Antipsychotics | 18 Participants | 16 Participants | 34 Participants |
| Psychiatric Medications Anxiolytics/Hypnotics | 21 Participants | 19 Participants | 40 Participants |
| Psychiatric Medications Benzodiazepines | 17 Participants | 33 Participants | 50 Participants |
| Psychiatric Medications Mood Stabilizers | 8 Participants | 12 Participants | 20 Participants |
| Psychiatric Medications Stimulants | 9 Participants | 16 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 56 Participants | 101 Participants |
| Region of Enrollment United States | 47 participants | 58 participants | 105 participants |
| Sex/Gender, Customized Female | 30 Participants | 39 Participants | 69 Participants |
| Sex/Gender, Customized Female to Male | 1 Participants | 0 Participants | 1 Participants |
| Sex/Gender, Customized Male | 16 Participants | 19 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 58 |
| other Total, other adverse events | 0 / 47 | 0 / 58 |
| serious Total, serious adverse events | 0 / 47 | 0 / 58 |
Outcome results
Primary
Percentage Change in General Anxiety Disorder 7-Item Assessment Score
Overall change in total General Anxiety Disorder 7-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assesses anxiety severity as baseline. Scores of 5, 10, and 15 are cut-off points for mild, moderate, and severe anxiety, respectively. All 7 items are summed to compute a total score, ranging from 0-21. Higher scores indicate more severe self-rated anxiety symptoms. Negative change from baseline implies a decrease in anxiety symptoms.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Data reported here includes subjects that had both first and final data point. As such, this group has a smaller sample size.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5.5cm Rule Group | Percentage Change in General Anxiety Disorder 7-Item Assessment Score | -33.6 percentage change from baseline | Standard Error 5.3 |
| F3 Group | Percentage Change in General Anxiety Disorder 7-Item Assessment Score | 27.5 percentage change from baseline | Standard Error 6.9 |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.p-value: 0.252t-test, 2 sided
Primary
Percentage Change in Montgomery-Asberg Depression Rating Scale Score
Overall change in total Montgomery-Asberg Depression Rating Scale score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This scale assesses depression severity at baseline. Scores of 8, 17, and 34 are cut-off points for mild, moderate, severe depression, respectively. This 10 item scale is summed to compute a total score, ranging from 0-60. Higher scores indicate more severe clinician-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Data reported here includes subjects that had both first and final data point. As such, this group has a smaller sample size.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5.5cm Rule Group | Percentage Change in Montgomery-Asberg Depression Rating Scale Score | -39.5 percentage of change from baseline | Standard Error 5.6 |
| F3 Group | Percentage Change in Montgomery-Asberg Depression Rating Scale Score | -37.8 percentage of change from baseline | Standard Error 5.6 |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.p-value: 0.828t-test, 2 sided
Primary
Percentage Change in Patient Health Questionnaire 9-Item Assessment Score
Overall change in total Patient Health Questionnaire 9-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assessment measures depression severity at baseline. Total scores of 5, 10, 15, and 20 represent markers for mild, moderate, moderately severe, and severe depression, respectively. All 9 items are summed to compute a total score, ranging from 0-27. Higher scores indicate more severe self-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5.5cm Rule Group | Percentage Change in Patient Health Questionnaire 9-Item Assessment Score | -38.7 percentage of change from baseline | Standard Error 5.1 |
| F3 Group | Percentage Change in Patient Health Questionnaire 9-Item Assessment Score | -39.1 percentage of change from baseline | Standard Error 4.7 |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.p-value: 0.945t-test, 2 sided
Primary
Response and Remission Rates on Montgomery-Asberg Depression Rating Scale
Comparison of the response rate (\>50% improvement) and remission rate (score \<10) for the MADRS between the 2 groups post-treatment.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Data reported here includes subjects that had both first and final data point. As such, this group has a smaller sample size.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5.5cm Rule Group | Response and Remission Rates on Montgomery-Asberg Depression Rating Scale | Responders | 43.3 percentage of participants |
| 5.5cm Rule Group | Response and Remission Rates on Montgomery-Asberg Depression Rating Scale | Remitters | 20.0 percentage of participants |
| F3 Group | Response and Remission Rates on Montgomery-Asberg Depression Rating Scale | Responders | 43.2 percentage of participants |
| F3 Group | Response and Remission Rates on Montgomery-Asberg Depression Rating Scale | Remitters | 18.9 percentage of participants |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.~A power analysis revealed that a total sample size of 144 would have 80% power when testing for differences between target groups at alpha = 0.05. Accounting for potential attrition, the study conservatively planned to enroll 200 participants, with a planned interim analysis after 100 participants were randomized.p-value: 0.994Chi-squared
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.~A power analysis revealed that a total sample size of 144 would have 80% power when testing for differences between target groups at alpha = 0.05. Accounting for potential attrition, the study conservatively planned to enroll 200 participants, with a planned interim analysis after 100 participants were randomized.p-value: 0.911Chi-squared
Primary
Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment
Comparison of the response rate (\>50% improvement) and remission rate (score \<5) for the Patient Health Questionnaire 9-Item Assessment between the 2 groups post-treatment.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5.5cm Rule Group | Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment | Responders | 36.6 percentage of participants |
| 5.5cm Rule Group | Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment | Remitters | 22.0 percentage of participants |
| F3 Group | Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment | Responders | 43.4 percentage of participants |
| F3 Group | Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment | Remitters | 20.8 percentage of participants |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.~A power analysis revealed that a total sample size of 144 would have 80% power when testing for differences between target groups at alpha = 0.05. Accounting for potential attrition, the study conservatively planned to enroll 200 participants, with a planned interim analysis after 100 participants were randomized.p-value: 0.505Chi-squared
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.~A power analysis revealed that a total sample size of 144 would have 80% power when testing for differences between target groups at alpha = 0.05. Accounting for potential attrition, the study conservatively planned to enroll 200 participants, with a planned interim analysis after 100 participants were randomized.p-value: 0.888Chi-squared
Primary
Response Rates on General Anxiety Disorder 7-Item Assessment
Comparison of the response rate (\>50% improvement) for the General Anxiety Disorder 7-Item Assessment between the 2 groups post-treatment.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Data reported here includes subjects that had both first and final data point. As such, this group has a smaller sample size.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5.5cm Rule Group | Response Rates on General Anxiety Disorder 7-Item Assessment | 27.3 percentage of participants |
| F3 Group | Response Rates on General Anxiety Disorder 7-Item Assessment | 30.2 percentage of participants |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.~A power analysis revealed that a total sample size of 144 would have 80% power when testing for differences between target groups at alpha = 0.05. Accounting for potential attrition, the study conservatively planned to enroll 200 participants, with a planned interim analysis after 100 participants were randomized.p-value: 0.778t-test, 2 sided
Secondary
Emotion Measures
T Score Changes in National Institutes of Health Toolbox Emotional Battery A T score of 50 corresponds to the population mean. Scores may range from 20-80 with a standard deviation of 10. Higher T scores indicate a higher endorsement of each domain. Here, we present changes in mean score from pre-treatment to post-treatment. In that way, a positive value represents a decrease in average T score, and vice versa.
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Only a subset of participants completed this task, so total sample size is much smaller.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5.5cm Rule Group | Emotion Measures | Emotional Support | -0.2 T Score | Standard Deviation 8.7 |
| 5.5cm Rule Group | Emotion Measures | Perceived Stress | 4.6 T Score | Standard Deviation 12 |
| 5.5cm Rule Group | Emotion Measures | Loneliness | 3.2 T Score | Standard Deviation 11.1 |
| 5.5cm Rule Group | Emotion Measures | Fear-Affect | 4.9 T Score | Standard Deviation 6.7 |
| 5.5cm Rule Group | Emotion Measures | Meaning & Purpose | -4.5 T Score | Standard Deviation 8 |
| 5.5cm Rule Group | Emotion Measures | Fear-Somatic Arousal | -1.1 T Score | Standard Deviation 10.9 |
| 5.5cm Rule Group | Emotion Measures | Perceived Rejection | -1.3 T Score | Standard Deviation 10.5 |
| 5.5cm Rule Group | Emotion Measures | Sadness | 7.0 T Score | Standard Deviation 14.5 |
| 5.5cm Rule Group | Emotion Measures | Instrumental Support | 3.9 T Score | Standard Deviation 9.4 |
| 5.5cm Rule Group | Emotion Measures | Anger-Affect | 6.5 T Score | Standard Deviation 11.1 |
| 5.5cm Rule Group | Emotion Measures | Perceived Hostility | 1.8 T Score | Standard Deviation 8.1 |
| 5.5cm Rule Group | Emotion Measures | Anger-Hostility | 2.1 T Score | Standard Deviation 12.2 |
| 5.5cm Rule Group | Emotion Measures | General Life Satisfaction | -2.7 T Score | Standard Deviation 7.1 |
| 5.5cm Rule Group | Emotion Measures | Anger-Physical Aggression | 3.4 T Score | Standard Deviation 9.2 |
| 5.5cm Rule Group | Emotion Measures | Negative Affect | 6.1 T Score | Standard Deviation 11.7 |
| 5.5cm Rule Group | Emotion Measures | Friendship | 0.1 T Score | Standard Deviation 5.3 |
| 5.5cm Rule Group | Emotion Measures | Social Satisfaction | 0.2 T Score | Standard Deviation 8.5 |
| 5.5cm Rule Group | Emotion Measures | Self-Efficacy | -1.6 T Score | Standard Deviation 6.3 |
| 5.5cm Rule Group | Emotion Measures | Psychological Well Being | -5.6 T Score | Standard Deviation 8.2 |
| 5.5cm Rule Group | Emotion Measures | Positive Affect | -7.2 T Score | Standard Deviation 9.4 |
| F3 Group | Emotion Measures | Psychological Well Being | -10.2 T Score | Standard Deviation 9.1 |
| F3 Group | Emotion Measures | Positive Affect | -10.4 T Score | Standard Deviation 8.9 |
| F3 Group | Emotion Measures | General Life Satisfaction | -9.2 T Score | Standard Deviation 9.6 |
| F3 Group | Emotion Measures | Meaning & Purpose | -6.7 T Score | Standard Deviation 9.5 |
| F3 Group | Emotion Measures | Emotional Support | -6.9 T Score | Standard Deviation 9 |
| F3 Group | Emotion Measures | Instrumental Support | -5 T Score | Standard Deviation 10.1 |
| F3 Group | Emotion Measures | Friendship | -5.4 T Score | Standard Deviation 7.5 |
| F3 Group | Emotion Measures | Loneliness | 5.8 T Score | Standard Deviation 8.5 |
| F3 Group | Emotion Measures | Perceived Rejection | 4.7 T Score | Standard Deviation 9.3 |
| F3 Group | Emotion Measures | Perceived Hostility | 4.3 T Score | Standard Deviation 9.1 |
| F3 Group | Emotion Measures | Anger-Physical Aggression | -0.6 T Score | Standard Deviation 4.9 |
| F3 Group | Emotion Measures | Self-Efficacy | -3.2 T Score | Standard Deviation 7.6 |
| F3 Group | Emotion Measures | Perceived Stress | 7.6 T Score | Standard Deviation 8.8 |
| F3 Group | Emotion Measures | Fear-Affect | 6.9 T Score | Standard Deviation 8.6 |
| F3 Group | Emotion Measures | Fear-Somatic Arousal | 4.4 T Score | Standard Deviation 9.4 |
| F3 Group | Emotion Measures | Sadness | 13.2 T Score | Standard Deviation 10.9 |
| F3 Group | Emotion Measures | Anger-Affect | 6.3 T Score | Standard Deviation 11.6 |
| F3 Group | Emotion Measures | Anger-Hostility | 2.7 T Score | Standard Deviation 8.8 |
| F3 Group | Emotion Measures | Negative Affect | 8.7 T Score | Standard Deviation 7.8 |
| F3 Group | Emotion Measures | Social Satisfaction | -7.2 T Score | Standard Deviation 9.4 |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Positive Affect.p-value: 0.278t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, General Life Satisfaction.p-value: 0.024t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Meaning \& Purpose.p-value: 0.439t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Emotional Support.p-value: 0.025t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Instrumental Support.p-value: 0.007t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Friendship.p-value: 0.014t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Loneliness.p-value: 0.398t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Perceived Rejection.p-value: 0.064t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Perceived Hostility.p-value: 0.368t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Self-Efficacy.p-value: 0.504t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Perceived Stress.p-value: 0.371t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Fear-Affect.p-value: 0.438t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Fear-Somatic Arousal.p-value: 0.096t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Sadness.p-value: 0.132t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Anger-Affect.p-value: 0.951t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Anger-Hostility.p-value: 0.852t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Anger-Physical Aggression.p-value: 0.083t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Negative Affect.p-value: 0.391t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Social Satisfaction.p-value: 0.014t-test, 2 sided
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures. Results below are for the subscale, Psychological Well Being.p-value: 0.109t-test, 2 sided
Secondary
Montreal Cognitive Assessment Score Changes
Change in Montreal Cognitive Assessment scores from baseline to final timepoint. Reported here as the mean difference in total Montreal Cognitive Assessment score from baseline to endpoint. Montreal Cognitive Assessment is used a screen for cognitive impairment, calculated by adding the points from each task, which range from 0-30. Higher scores indicate little to no cognitive impairment 26 or above: Normal cognition 18-25: Mild cognitive impairment 10-17: Moderate cognitive impairment Fewer than 10: Severe cognitive impairment
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Population: Data reported here includes subjects that had both first and final data point. As such, this group has a smaller sample size.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5.5cm Rule Group | Montreal Cognitive Assessment Score Changes | .59 score on a scale | Standard Deviation 2.3 |
| F3 Group | Montreal Cognitive Assessment Score Changes | .56 score on a scale | Standard Deviation 1.8 |
Comparison: The null hypothesis of this study was that there would be no differences between targets across all measures.p-value: 0.951t-test, 2 sided
Post Hoc
General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model
An exploratory analysis to investigate between-group differences in trajectory of improvement as measured by group by time interactions. This assesses anxiety severity as baseline. Scores of 5, 10, and 15 are cut-off points for mild, moderate, and severe anxiety, respectively. All 7 items are summed to compute a total score, ranging from 0-21. Higher scores indicate more severe self-rated anxiety symptoms. Negative change from baseline implies a decrease in anxiety symptoms.
Time frame: Baseline to weekly timepoints
Population: All randomized participants were included in this analysis. Weekly timepoints have different ns due to dropouts and/or missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 2 | 10.9 mean GAD-7 total score | Standard Deviation 5.4 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 4 | 9.7 mean GAD-7 total score | Standard Deviation 4.9 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 1 | 12.3 mean GAD-7 total score | Standard Deviation 5.1 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 5 | 9.6 mean GAD-7 total score | Standard Deviation 5.5 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 3 | 10.7 mean GAD-7 total score | Standard Deviation 5.7 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 6 | 9.0 mean GAD-7 total score | Standard Deviation 5.6 |
| 5.5cm Rule Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | First Visit | 14.3 mean GAD-7 total score | Standard Deviation 4.7 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 6 | 10.0 mean GAD-7 total score | Standard Deviation 6.6 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | First Visit | 13.5 mean GAD-7 total score | Standard Deviation 5.2 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 1 | 12.6 mean GAD-7 total score | Standard Deviation 5.2 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 2 | 11.3 mean GAD-7 total score | Standard Deviation 5.7 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 3 | 10.8 mean GAD-7 total score | Standard Deviation 5.6 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 4 | 10.6 mean GAD-7 total score | Standard Deviation 6.4 |
| F3 Group | General Anxiety Disorder 7-Item Assessment Linear Mixed Effects Model | Week 5 | 10.0 mean GAD-7 total score | Standard Deviation 6.5 |
p-value: 0.051Mixed Models Analysis
Post Hoc
Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model
An exploratory analysis to investigate between-group differences in trajectory of improvement as measured by group by time interactions. This scale assesses depression severity at baseline. Scores of 8, 17, and 34 are cut-off points for mild, moderate, severe depression, respectively. This 10 item scale is summed to compute a total score, ranging from 0-60. Higher scores indicate more severe clinician-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Time frame: Baseline to biweekly timepoints
Population: All randomized participants were included in this analysis. Weekly timepoints have different ns due to dropouts and/or missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5.5cm Rule Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Evaluation | 29.1 mean MADRS total score | Standard Deviation 6.9 |
| 5.5cm Rule Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 2-3 Follow-up | 24.2 mean MADRS total score | Standard Deviation 8.1 |
| 5.5cm Rule Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 4-5 Follow-up | 18.4 mean MADRS total score | Standard Deviation 9.3 |
| 5.5cm Rule Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 6-7 Follow-up | 15.3 mean MADRS total score | Standard Deviation 8.8 |
| F3 Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 6-7 Follow-up | 16.4 mean MADRS total score | Standard Deviation 9.7 |
| F3 Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Evaluation | 29.8 mean MADRS total score | Standard Deviation 5.9 |
| F3 Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 4-5 Follow-up | 19.6 mean MADRS total score | Standard Deviation 8.7 |
| F3 Group | Montgomery-Asberg Depression Rating Scale Linear Mixed Effects Model | Week 2-3 Follow-up | 22.0 mean MADRS total score | Standard Deviation 7.2 |
p-value: 0.963Mixed Models Analysis
Post Hoc
Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model
An exploratory analysis to investigate between-group differences in trajectory of improvement as measured by group by time interactions. This assessment measures depression severity at baseline. Total scores of 5, 10, 15, and 20 represent markers for mild, moderate, moderately severe, and severe depression, respectively. All 9 items are summed to compute a total score, ranging from 0-27. Higher scores indicate more severe self-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Time frame: Baseline to Weeks 1 through 6, assessed weekly
Population: All randomized participants were included in this analysis. Weekly timepoints have different ns due to dropouts and/or missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 2 | 14.6 mean PHQ-9 total score | Standard Deviation 6.3 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 4 | 13.2 mean PHQ-9 total score | Standard Deviation 6.3 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 1 | 15.7 mean PHQ-9 total score | Standard Deviation 6.2 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 5 | 12.5 mean PHQ-9 total score | Standard Deviation 6.3 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 3 | 14.2 mean PHQ-9 total score | Standard Deviation 6.7 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 6 | 10.7 mean PHQ-9 total score | Standard Deviation 6.7 |
| 5.5cm Rule Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | First Visit | 18.8 mean PHQ-9 total score | Standard Deviation 4.3 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 6 | 11.2 mean PHQ-9 total score | Standard Deviation 7.5 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | First Visit | 17.8 mean PHQ-9 total score | Standard Deviation 4.9 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 1 | 16.2 mean PHQ-9 total score | Standard Deviation 5.9 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 2 | 14.4 mean PHQ-9 total score | Standard Deviation 6.3 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 3 | 12.6 mean PHQ-9 total score | Standard Deviation 6.4 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 4 | 13.0 mean PHQ-9 total score | Standard Deviation 6.5 |
| F3 Group | Patient Health Questionnaire 9-Item Assessment Linear Mixed Effects Model | Week 5 | 11.8 mean PHQ-9 total score | Standard Deviation 7.1 |
p-value: 0.231Mixed Models Analysis