Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)

Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 1 Day 4 minus mean score at baseline. Week 1 Day 4 : Change from baseline to the end of the efficacy period ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) total score .Responders at Day 4 will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders at Day 4. Each patient's total score is his/her own reference for determining a decrease of 50% or more.

Time frame: Week 1 Day 4

Population: Subjects in the All Randomized set who completed at least one treatment session and had at least one post baseline primary efficacy assessment.

Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from Day 11: mean score at Week 2 Day 11 minus mean score at Day 4. To determine if subjects with TRD who are non-responders to 0, 20 or 60 minutes of LFMS on Day 4 may respond to 120 minutes of LFMS at the end of Day 11. Responders will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders. Each patient's total score is his/her own reference for determining a decrease of 50% or more.

Time frame: Day 11 (Week 2)

Population: Only non-responders at end of Day 4 comprise this Wk 2 analysis . (Non-responders were defined as those who didn't reach a decrease in 6-item Hamilton Rating Scale for Depression (HAM-D6) total score of 50% compared to baseline Day 1, Week 1). 41 subjects entered Week 2: 1 subject withdrew consent on Day 8 and was not part of the Full Analysis Set.

To determine the persistence of response to LFMS therapy during a four-week follow-up period in subjects who were responders at Day 4. Persistence of response was achieved if during Week 2 post baseline visits and follow-up visits subjects' 6-item Hamilton Rating Scale for Depression (HAM-D6) total scores were lower than or equal to 50% of the baseline ( Day1 Week1) scores. Non-responder imputation method was used where missing post-baseline dichotomous (yes or no) were imputed as non-responder. Logistic regression model used to compare treatment groups for each visit, where the model considers the treatment, age and gender as covariates.

Time frame: Day 42

Population: Subjects who were HAM-D6 Day 4 responders, defined as those subjects who achieved a 50% or greater decrease in their HAM-D6 total score compared to Baseline ( Day1, Wk 1).

The MADRS is a 10-item checklist designed to measure the overall severity of depressive symptoms in subjects with Major Depressive Disorder (MDD). Individual items are rated on a scale of 0 to 6 in which a score of 6 represents the most severe symptoms for each item assessed. The total score ranges from 0 to 60. Remission of depression based on the MADRS is defined as a subject with a MADRS total score of ≤11 at endpoint. A responder on the MADRS is defined as a 50% or greater reduction from baseline in total MADRS score

Time frame: Day 4 Week 1

Population: Full Analysis Set, Week1

The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Used as a psychometric scale, the PANAS can show relationships between positive and negative affect with personality stats and traits. Descriptors are used to define their meanings. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).To calculate the positive affect score, added scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10-50, which higher scores representing higher levels of positive affect, or the extent to which the individual feels enthusiastic, active and alert.

Time frame: Day 4 Week 1

Population: Full Analysis Set (Week 1).

The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome treated Item #2 as random missing data.

Time frame: Day 4, Week 1

Population: Full analysis set, Week 1.Item #2 was incorrectly listed as Disinterested instead of Distressed.resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details.

The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome treated Incorrect Item #2 where Item #2 data was removed.

Time frame: Day 4

Population: Full analysis set, Week 1.Item #2 was incorrectly listed as Disinterested instead of Distressed.resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details.

The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome approach took Incorrect Item #2 and imputed using worst possible value.

Time frame: Day 4, Week 1

Population: Full analysis set, Week 1.Item #2 was incorrectly listed as Disinterested instead of Distressed.resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details.