Combined TMS and Brief Cognitive Behavioral Therapy to Reduce Suicide

Combined Transcranial Magnetic Stimulation and Brief Cognitive Therapy to Reduce Suicide Behavior in High-Risk Veterans

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03952468

Enrollment

Registered

2019-05-16

Start date

2019-11-04

Completion date

2024-04-30

Last updated

2025-09-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Suicide

Keywords

suicide prevention, Veterans

Brief summary

High rates of Veteran suicide remain a tragedy. Rates of Veteran suicide have not decreased for 10 years, despite the best efforts of the field. Those interventions that do exist have only modest effects, which are simply insufficient for the magnitude of the problem. This proposal will combine two treatments - brief cognitive behavioral therapy (BCBT) and repetitive transcranial magnetic stimulation (TMS). Both of these interventions can reduce suicide and are available at Veterans Affairs Medical Centers across the country, yet to date no one has combined these therapies. This proposal will test the effect of this combination, and, if successful, will lead to a novel yet implementable new treatment to reduce Veteran suicide.

Detailed description

The goal of the proposed study is to test the effect of adding Transcranial Magnetic Stimulation (TMS) to Brief Cognitive Behavioral Therapy (BCBT) to reduce Veterans' rates of suicide ideation and related behaviors. Over 20 Veterans die each day of suicide and rates have not appreciably decreased in the last ten years. BCBT is a well-established and efficacious treatment that is an extension of Cognitive Behavioral Therapy, a treatment that is widely implemented across VA health care systems. However, not all patients respond to BCBT. Thus finding ways to enhance treatment efficacy for reducing suicide is critical. Transcranial Magnetic Stimulation (TMS) may be an optimal treatment to use in conjunction with psychotherapy. TMS is a noninvasive technique that uses a pulsed magnetic field to induce neuronal depolarization in a targeted brain region, typically the left dorsolateral prefrontal cortex. TMS can reduce psychiatric symptoms associated with suicide risk in Veterans, including depression and PTSD. Furthermore, TMS is not associated with the systemic and costly side effects associated with medications used for these disorders (e.g., weight gain, diabetes, sexual side effects). The primary objective of this study is to conduct a fully-powered randomized controlled trial evaluating the effect of adding a standard TMS course of treatment to BCBT to reduce suicide behaviors in a sample of Veterans hospitalized for suicide behavior. One hundred and thirty (130) Veterans admitted to the psychiatric unit for suicide ideation or attempts will be randomly assigned to either active TMS plus BCBT or to sham TMS plus BCBT. Participants will be assessed at baseline, post treatment, six, and 12 months post hospital discharge. Efficacy of the program will be determined by examining a primary suicide composite outcome and several secondary outcomes including suicide attempt, time to first attempt, number of re-hospitalizations and severity and severity of suicidal ideation. Secondary analyses will be conducted to help identify the types of patients who will receive the most benefit from the addition of TMS to BCBT Brief Cognitive Behavioral Therapy for suicide. If successful, this study would result in a combined treatment to decrease suicide ideation and related behaviors. The proposal addresses HSRD post-deployment health priority, specifically suicide prevention and is innovative in that it will be the first study to examine efficacy of combined treatment specifically for suicide prevention.

Interventions

DEVICETranscranial Magnetic Stimulation

Administration of rapidly fluctuating magnetic field, delivered over the dorsolateral prefrontal cortex.

OTHERBrief Cognitive Behavioral Therapy

BCBT is a well-established and efficacious treatment that is an extension of Cognitive Behavioral Therapy, a treatment that is widely implemented across VA health care systems.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Masking description

Prior to each TMS session, un-blinded study staff will attach the appropriate (i.e., active or sham) coil according to the participants' randomization code (obtained from the urn randomization computer program). This will facilitate triple blind stimulation, where the participant, TMS provider, and outcome rater are blind to group assignation.

Intervention model description

130 Veterans admitted to the Providence VAMC psychiatric inpatient unit due to suicide attempt or ideation with intent to make an attempt will be recruited and randomly assigned to receive: a) active TMS+BCBT or b) sham TMS+BCBT. Both interventions will begin within the week following hospital discharge, and Veterans will be followed for 12 months post-discharge.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

-Suicide attempt or suicidal ideation with intent to make a suicide attempt within 48 hours of hospitalization as indicated on the hospital chart and confirmed by administration of the C-SSRS.

Exclusion criteria

* Primary psychotic disorder * Bipolar disorder * Cognitive impairment which would interfere with adequate participation in the project (MMSE \< 20). * For safety, participants must meet established screening criteria safety during MRI, which is implemented as a conservative measure given the application of TMS in this population, since MRI involves magnetic fields at similar intensity to those emitted from the stimulation coil. These measures require a patient not having the following (unless MRI-safe): * Cardiac pacemaker * Implanted device (deep brain stimulation) or metal in the brain, cervical spinal cord, or upper thoracic spinal cord. * TMS-specific exclusions are: * pregnancy/lactation, or planning to become pregnant during the study * lifetime history of moderate or severe traumatic brain injury (TBI) * Current unstable medical conditions * Current (or past if appropriate) significant neurological disorder * Lifetime history seizure disorder * Primary or secondary CNS tumors * Stroke * Cerebral aneurysm. * Other exclusions are conditions that would like to be worsened by TMS, such as bipolar disorder * Place Veterans at greater risk of seizures from TMS, such as severe and uncontrolled substance use disorder * Inability to participate in CBT * Other conditions or circumstance that, in the opinion of the investigator team, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments

Design outcomes

Primary

Measure	Time frame	Description
Columbia Suicide Severity Rating Scale (CSSRS) (Suicide Composite)	Baseline, endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up	The Columbia suicide severity rating scale is an interview-administered assessment of suicide ideation and behavior. The full CSSRS interview consists of two subscales, an ideation and behavior subscale. The primary outcome measure for this study utilized the behavior subscale. A study-created composite score was calculated by adding the total number of: 1) suicide attempts, 2) interrupted attempts, and 3) aborted attempts in the specified time frame. At baseline total number of behaviors covered lifetime number of total behaviors prior to baseline. Each subsequent assessment period assesses total number of behaviors since time of last assessment (e.g., endpoint = total number of behaviors from baseline to end of 12-week BCBT course, 6-month follow up = total number of behaviors from endpoint to 6 months post-baseline, 12 months = total number of behaviors from 6 month follow up to 12 month follow up.

Secondary

Measure	Time frame	Description
Beck Scale for Suicide Ideation (BSSI)	Baseline, endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up	The BSSI is a 21-item measure designed to assess the severity of suicidal thoughts in the week prior to evaluation. The first 5 items are screeners (wish to live, wish to die, and desire to attempt suicide), followed by 14 items to assess suicidal risk factors. The last 2 items capture previous suicide attempts. Each item is scored based on an ordinal scale from 0-2 and the total score range is 0-38 with higher scores indicating greater severity. The SSI total score is obtained by adding up the ratings (0-2) from the first 19 items.
The Longitudinal Interval Follow-up Evaluation (LIFE): Psychiatric Status Rating Scale for Suicidal Ideation	Endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up	The Longitudinal Interval Follow-up Evaluation (LIFE) is a timeline follow up interview measure that is administered at each of the assessment period. Participants are asked to describe their weekly suicidal thoughts and interviewers rate them on a 6-point Likert score ranging from 1 (not at all) to 6 (Extreme: has made preparations for a potentially serious suicide attempt). Data is then converted into the presence/absence of suicidal thoughts for each week of the follow up period. Data reported includes the mean number of weeks with reported suicidal thoughts (scores above 2).
Change in World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)	Baseline, endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up	The WHODAS 2.0 is a 36-question, self-administered questionnaire and generic assessment instrument for health and disability that covers six domains: Cognition (items 3 and 6), Mobility (items 1 and 7), Self-care (items 8 and 9), Getting Along (items 10 and 11), Life Activities (items 2 and 12), and Participation (items 4 and 5). Items are rated from None, Mild, Moderate, Severe, to Extreme or cannot do, indicating difficulty over the past month. Total score is calculated by summing the item scores and then converted into a standardized score ranging from 0-100 with higher scores indicating greater disability.
Treatment History Interview THI: Emergency Services	Endpoint (following a 12-week course of BCBT), 6-month follow-up, 12-month follow-up	The THI is an interview used to collect information about psychotherapy, hospitalizations, medical treatment, pharmacotherapy, and other means of psychologically-related help that a person may use. For this study we assessed the use of emergency services (emergency room visits for psychiatric reasons and hospitalizations for psychiatric reasons). Outcome was the number of times a participant used either emergency department or was hospitalized for mental health reasons.
Brief Symptom Inventory: Psychiatric Symptoms	Baseline, endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up	The BSI is a 53-item self-report questionnaire developed by Derogatis and Melisarotos to measure psychological distress and assess the severity of symptom across the following dimensions: Somatization, Obsession-compulsion, interpersonal sensitivity , depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism. Items are rated on a 5-point Likert scale from 0-4. The Global severity index (GSI) was used and reported. GSI is a mean score for all items across all dimensions. Higher scores are indicative of greater psychological distress.

Countries

United States

Participant flow

Pre-assignment details

Following enrollment, 22 Veterans were not randomized. Of these 22 Veterans, 7 were ineligible, 6 were lost to contact, and 9 requested to withdraw participation due to starting residential treatment or work/scheduling concerns.

Participants by arm

Arm	Count
Active TMS + Brief Cognitive Behavioral Therapy Combined transcranial magnetic stimulation and brief cognitive behavioral therapy for suicide Transcranial Magnetic Stimulation: Administration of rapidly fluctuating magnetic field, delivered over the dorsolateral prefrontal cortex. Brief Cognitive Behavioral Therapy: BCBT is a well-established and efficacious treatment that is an extension of Cognitive Behavioral Therapy, a treatment that is widely implemented across VA health care systems.	18
Sham TMS + Brief Cognitive Behavioral Therapy Sham Transcranial magnetic stimulation and brief cognitive behavioral therapy for suicide Transcranial Magnetic Stimulation: Administration of rapidly fluctuating magnetic field, delivered over the dorsolateral prefrontal cortex. Brief Cognitive Behavioral Therapy: BCBT is a well-established and efficacious treatment that is an extension of Cognitive Behavioral Therapy, a treatment that is widely implemented across VA health care systems.	15
Total	33

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Death	0	1
Overall Study	Lost to Follow-up	3	4
Overall Study	Physician Decision	1	0
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	Active TMS + Brief Cognitive Behavioral Therapy	Total	Sham TMS + Brief Cognitive Behavioral Therapy
Age, Continuous	47.8 Years STANDARD_DEVIATION 10.9	49.0 Years STANDARD_DEVIATION 12.1	50.4 Years STANDARD_DEVIATION 13.6
AUDIT-10 (Alcohol Use Disorders Identification Test)	9.83 units on a scale STANDARD_DEVIATION 11.98	9.67 units on a scale STANDARD_DEVIATION 11.62	9.47 units on a scale STANDARD_DEVIATION 11.58
Beck Hopelessness Scale (BHS)	11.5 units on a scale STANDARD_DEVIATION 6.71	11.27 units on a scale STANDARD_DEVIATION 6.5	11.0 units on a scale STANDARD_DEVIATION 6.46
Beck Scale for suicide ideation (BSSI)	15.83 units on a scale STANDARD_DEVIATION 8.45	15.97 units on a scale STANDARD_DEVIATION 6.82	16.13 units on a scale STANDARD_DEVIATION 4.42
Brief Symptom Inventory (BSI): Psychiatric Symptoms	2.10 Mean score (GSI) STANDARD_DEVIATION 1.13	1.99 Mean score (GSI) STANDARD_DEVIATION 1.08	1.85 Mean score (GSI) STANDARD_DEVIATION 1.04
CSSRS ideation severity, lifetime	4.56 units of a scale STANDARD_DEVIATION 0.51	4.48 units of a scale STANDARD_DEVIATION 0.51	4.4 units of a scale STANDARD_DEVIATION 0.51
CSSRS ideation severity, past two weeks	4.56 units on a scale (0-5) STANDARD_DEVIATION 0.51	4.45 units on a scale (0-5) STANDARD_DEVIATION 0.56	4.33 units on a scale (0-5) STANDARD_DEVIATION 0.62
CSSRS (Lifetime number of attempts)	2.78 number of attempts STANDARD_DEVIATION 5.93	4.00 number of attempts STANDARD_DEVIATION 7.13	5.47 number of attempts STANDARD_DEVIATION 8.33
CSSRS lifetime total number of suicide behaviors composite	2.94 number of behaviors STANDARD_DEVIATION 5.89	4.58 number of behaviors STANDARD_DEVIATION 8.08	6.53 number of behaviors STANDARD_DEVIATION 9.98
CSSRS past two week attempts	0.39 number of attempts STANDARD_DEVIATION 0.7	0.33 number of attempts STANDARD_DEVIATION 0.74	0.27 number of attempts STANDARD_DEVIATION 0.8
CSSRS past two week behavior composite	0.61 number of suicide behaviors STANDARD_DEVIATION 0.92	0.48 number of suicide behaviors STANDARD_DEVIATION 0.87	0.33 number of suicide behaviors STANDARD_DEVIATION 0.82
DUDIT (Drug Use Disorders Identification Test)	4.67 units on a scale STANDARD_DEVIATION 6.51	3.82 units on a scale STANDARD_DEVIATION 5.51	2.80 units on a scale STANDARD_DEVIATION 4
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants	32 Participants	15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Inventory of Depressive Symptomatology-Self Report (IDS-SR)	44.0 units on a scale STANDARD_DEVIATION 17.44	42.12 units on a scale STANDARD_DEVIATION 26.8	39.87 units on a scale STANDARD_DEVIATION 15.71
McLean Borderline Personality screen (MSI-BPD)	13 Participants	21 Participants	8 Participants
PTSD Checklist	49.11 units on a scale STANDARD_DEVIATION 20.46	46.64 units on a scale STANDARD_DEVIATION 21.86	43.67 units on a scale STANDARD_DEVIATION 23.79
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	15 Participants	27 Participants	12 Participants
Region of Enrollment United States	18 Participants	33 Participants	15 Participants
SCID Module A Current Hypomanic Episode	0 Participants	0 Participants	0 Participants
SCID Module A Current Major Depressive Episode	14 Participants	27 Participants	13 Participants
SCID Module A Did not meet diagnostic criteria	2 Participants	3 Participants	1 Participants
SCID Module A Past Hypomanic Episode	0 Participants	0 Participants	0 Participants
SCID Module A Past Major Depressive Episode	2 Participants	3 Participants	1 Participants
Sex: Female, Male Female	3 Participants	5 Participants	2 Participants
Sex: Female, Male Male	15 Participants	28 Participants	13 Participants
World Health Organization Disability Assessment Schedule (WHODAS-2.0)	50.89 standardized scores STANDARD_DEVIATION 30.2	49.67 standardized scores STANDARD_DEVIATION 26.2	48.20 standardized scores STANDARD_DEVIATION 23.03

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 18	1 / 15
other Total, other adverse events	11 / 18	6 / 15
serious Total, serious adverse events	6 / 18	5 / 15

Outcome results

Primary

Columbia Suicide Severity Rating Scale (CSSRS) (Suicide Composite)

The Columbia suicide severity rating scale is an interview-administered assessment of suicide ideation and behavior. The full CSSRS interview consists of two subscales, an ideation and behavior subscale. The primary outcome measure for this study utilized the behavior subscale. A study-created composite score was calculated by adding the total number of: 1) suicide attempts, 2) interrupted attempts, and 3) aborted attempts in the specified time frame. At baseline total number of behaviors covered lifetime number of total behaviors prior to baseline. Each subsequent assessment period assesses total number of behaviors since time of last assessment (e.g., endpoint = total number of behaviors from baseline to end of 12-week BCBT course, 6-month follow up = total number of behaviors from endpoint to 6 months post-baseline, 12 months = total number of behaviors from 6 month follow up to 12 month follow up.

Time frame: Baseline, endpoint (end of 12-week BCBT course), 6-month follow-up, and 12 month follow up