Trial Outcomes & Findings for Intensive TMS for Bipolar Depression (NCT NCT05228457)

Last Updated: 2025-03-12

Results Overview

The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline, on each of the five treatment days and post TMS.

Recruitment status

COMPLETED

Study phase

Target enrollment

34 participants

Primary outcome timeframe

Through study completion, approximately 1 week

Results posted on

2025-03-12

Participant Flow

Thirty-four participants were assessed for eligibility. Of these, eight did not meet the inclusion criteria and were excluded: three participants displayed manic symptoms at screening, four did not meet the criteria for major depression, and one did not meet the criteria for bipolar disorder.

Participant milestones

Participant milestones
Measure	Active Transcranial Magnetic Stimulation Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Active TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of TMS treatment for a total of 10 sessions a day.	Sham Transcranial Magnetic Stimulation Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Sham TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.
Overall Study STARTED	13	13
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Transcranial Magnetic Stimulation Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Active TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of TMS treatment for a total of 10 sessions a day.	Sham Transcranial Magnetic Stimulation Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Sham TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Transcranial Magnetic Stimulation n=13 Participants Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.	Sham Transcranial Magnetic Stimulation n=13 Participants Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.	Total n=26 Participants Total of all reporting groups
Age, Continuous	45 years STANDARD_DEVIATION 14.7 • n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	44 years STANDARD_DEVIATION 19.2 • n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	44.5 years STANDARD_DEVIATION 16.8 • n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Sex: Female, Male Female	6 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.	6 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.	12 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.
Sex: Female, Male Male	6 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.	6 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.	12 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) Asian	1 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	2 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	3 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) Black or African American	2 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	1 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	3 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) White	9 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	9 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	18 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) More than one race	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=12 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis	0 Participants n=24 Participants • Thirteen participants were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis

PRIMARY outcome

Timeframe: Through study completion, approximately 1 week

Population: Thirteen participants (age between 18-70)were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.

Outcome measures

Outcome measures
Measure	Active Transcranial Magnetic Stimulation n=12 Participants Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Active TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.	Sham Transcranial Magnetic Stimulation n=12 Participants Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Sham TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) baseline	30.4 score on a scale Standard Deviation 4.81	28 score on a scale Standard Deviation 5.41
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) treatment end	10.5 score on a scale Standard Deviation 6.76	25.3 score on a scale Standard Deviation 6.74
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) Day 1	26.7 score on a scale Standard Deviation 2.27	26.8 score on a scale Standard Deviation 6.19
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) Day 2	20.3 score on a scale Standard Deviation 6.27	25.7 score on a scale Standard Deviation 5.55
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) Day 3	16.3 score on a scale Standard Deviation 7.65	24.3 score on a scale Standard Deviation 5.94
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) Day 4	11.3 score on a scale Standard Deviation 7.23	24.8 score on a scale Standard Deviation 4.81
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) Day 5	10.2 score on a scale Standard Deviation 7.56	25.3 score on a scale Standard Deviation 6.74

SECONDARY outcome

Timeframe: Upon study completion, approximately 1 week

Population: Thirteen participants (age between 18-70) were randomized to receive active TMS, and thirteen were randomized to receive sham TMS. One participant from each group withdrew from the study due to time commitment constraints, resulting in their exclusion from the analysis. Therefore, twelve participants from each group completed the study and were included in the final analysis.

The secondary outcome will be the change in the correlation between the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC) with the Montgomery-Åsberg Depression Rating Scale (MADRS), as assessed through MRI scans conducted at baseline and post-stimulation. Additionally, the change in the correlation within the entire Default Mode Network (DMN) intraconnectivity and MADRS will be measured for both groups (Active vs. Sham). The correlation is measured on a scale from -1 to +1, where -1 indicates the highest negative anticorrelation, +1 represents the highest positive correlation, and 0 signifies no correlation. MADRS is used to assess the clinical effect.

Outcome measures

Outcome measures
Measure	Active Transcranial Magnetic Stimulation n=12 Participants Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Active TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.	Sham Transcranial Magnetic Stimulation n=12 Participants Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Sham TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.
Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects Correlation between the whole Default Mode Network (DMN) intraconnectivity and MADRS	0.15 correlation coefficient Interval -1.0 to 1.0	-0.43 correlation coefficient Interval -1.0 to 1.0
Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects Correlation between connectivity between (DLPFC) vs (sgACC) and MADRS.	-0.63 correlation coefficient Interval -1.0 to 1.0	0.33 correlation coefficient Interval -1.0 to 1.0

Adverse Events

Active Transcranial Magnetic Stimulation

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Sham Transcranial Magnetic Stimulation

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Active Transcranial Magnetic Stimulation n=13 participants at risk Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Active TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.	Sham Transcranial Magnetic Stimulation n=13 participants at risk Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Intensive intermittent theta-burst stimulation (iTBS): Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. Sham TMS was administered every day for five days over the course of nine hours. Every hour, the participant received nine minutes of sham TMS treatment and total of 10 sessions a day.
Nervous system disorders Headache	38.5% 5/13 • Number of events 5 • For each participant, adverse events were recorded from baseline to the end of participation, typically about 6 weeks. This randomized clinical trial was conducted from March 2022 to February 2024, with all adverse event data collected throughout this period.	15.4% 2/13 • Number of events 2 • For each participant, adverse events were recorded from baseline to the end of participation, typically about 6 weeks. This randomized clinical trial was conducted from March 2022 to February 2024, with all adverse event data collected throughout this period.
Nervous system disorders dizziness	7.7% 1/13 • Number of events 1 • For each participant, adverse events were recorded from baseline to the end of participation, typically about 6 weeks. This randomized clinical trial was conducted from March 2022 to February 2024, with all adverse event data collected throughout this period.	0.00% 0/13 • For each participant, adverse events were recorded from baseline to the end of participation, typically about 6 weeks. This randomized clinical trial was conducted from March 2022 to February 2024, with all adverse event data collected throughout this period.

Additional Information

Walid Makhoul

University of Pennsylvania

Phone: 215-573-2409

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place