Transcranial Magnetic Stimulation (TMS) for Suicidal Ideation

A Pilot Safety and Feasibility Study of High Dose Left Prefrontal Transcranial Magnetic Stimulation (TMS) to Rapidly Stabilize Suicidal Patients With PTSD

The purpose of this study is to determine whether transcranial magnetic stimulation (TMS) is effective in the treatment of suicidal thinking in individuals with a depressive episode and either posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (TBI), or both conditions.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury; Posttraumatic Stress Disorder; Depressive Episode
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: Transcranial Magnetic Stimulation - Sham Comparator

Detailed Description

Evidence suggests that depression in general, and suicidal ideation in particular, results from a dysfunctional regulatory pathway involving prefrontal cortical governance over limbic activity. Repeated daily non-invasive stimulation of the prefrontal cortex with TMS would theoretically strengthen and reset this cortical control pathway and reduce suicidal ideation and restore healthy circuit behavior.

The aim of the current study is to assess the efficacy of TMS therapy in the treatment of suicidal ideation in patients with depressive episode(s) and either PTSD or mild TBI or both. It is hypothesized that participants who receive repetitive TMS (Group 1) relative to sham treatment (Group 2) three times daily over three days will evidence more improvement in suicidal ideation from baseline to the end of day 3. Participants will be followed for six months following treatment to assess safety and long-term efficacy of TMS.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Veteran inpatients aged 18-70 years inclusive, with a depressive episode.

2. Must also have either or both

   1. a diagnosis of PTSD as defined by DSM-IV supported by the SCID, or
   2. a diagnosis of mild TBI, either complicated (i.e., with imaging abnormalities) or uncomplicated, as defined by INTRuST criteria. The American Congress of Rehabilitation Medicine (ACRM) definition of mild TBI will be utilized for this study (Kay et al., 1993). That definition will be operationalized using the INTRuST Screening Instrument.
3. Admitted because of suicidal ideation.
4. SSI score > 12.
5. HRSD question #3 > 3.
6. Female subjects of childbearing potential must have a negative urine pregnancy test.
7. Comorbid (non-principal) diagnoses of psychiatric disorders not explicitly listed in the following Exclusion Criteria section are generally permitted (with final eligibility determination by Site Principal Investigator clinical assessment).
8. Subjects must be able to speak English and complete study forms, adhere to treatment regimens, and be willing to return for regular visits.
9. After full explanation of the study, subjects must demonstrate their willingness to participate by signing the informed consent form.

Exclusion Criteria:

1. Subjects who have clinically unstable medical disease (cardiovascular, renal, gastrointestinal, pulmonary, metabolic, endocrine, other); CNS disease deemed progressive; moderate or severe traumatic brain injury (TBI). Patients with mild TBI, however, will not be excluded from study participation. The ACRM definition of mild TBI will be utilized for this study (Kay et al., 1993). That definition will be operationalized using the INTRuST TBI Screening Instrument.
2. Females who are pregnant or currently breast feeding.
3. Current or history of schizophrenia or other psychotic disorder (except psychosis NOS when the presence of sensory hallucinations are clearly related to the subject's trauma), bipolar Type I disorder, or dementia (vascular, Alzheimer's disease, other types). Patients with bipolar Type II disorder will not be excluded.
4. Subjects who repeatedly abused or were dependent upon drugs (excluding nicotine and caffeine) within 6 days of study entry will be excluded, (with the exception of alcohol abuse which, at the discretion of the primary site investigator, may be permitted*).
5. Subjects actively participating (or planning to enroll) in an evidence-based exposure/cognitive treatment for PTSD during the trial, or who have been enrolled in one during the past 6 weeks; participation in other psychotherapeutic modalities must have been stable for 3 months prior to enrollment and remain stable throughout participation.
6. Subjects currently taking medications that have short half-lives, lower the seizure threshold, and do not have evidence of antidepressant efficacy. These include high dose theophylline, or stimulants such as methylphenidate. Patients taking buproprion have to be on a stable dose and take less than or equal to 300 mg/day. Stable means the same dose for 5 half-lives.
7. Subjects with metal in their head (other than dental implants), implanted devices in their head (shunts, cochlear implants).
8. Subjects with a history of seizures or a seizure disorder.
9. Subjects with borderline personality disorder or who have clear evidence of secondary gain as a reason for admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham	Device: Transcranial Magnetic Stimulation - Sham Comparator; The control group will receive an identical dosing schedule of "sham" repetitive TMS over three days.
Experimental: TMS	Device: Transcranial Magnetic Stimulation; Group 1: The treatment group will receive the following dose of repetitive TMS delivered over the left prefrontal cortex: 10 Hz, 120% Motor Threshold, 5 second pulse train, 10 second intertrain (IT) interval, 30 minutes of treatment, 6000 pulses per session; three sessions each day (18,000 stimuli) for three days for a total of 54,000 stimuli.; Other Names: Neuronetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Scale of Suicidal Ideation	baseline to Day 3 of TMS treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	-adverse events, study study discontinuation due to adverse events, & decrease in cognitive function as measured by significant change on neuropsychological measures	baseline through 6-month follow-up.
long-term efficacy of TMS	-length of current hospital stay along with Scale of Suicidal Ideation score, rehospitalization rates, and suicide completion rates over 6 months of follow-up	baseline through 6-month follow-up

Collaborators and Investigators

• Sponsor: INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
• Collaborators: Medical University of South Carolina; University of California, San Diego; U.S. Army Medical Research and Development Command; Walter Reed National Military Medical Center; Ralph H. Johnson VA Medical Center

Publications and helpful links

General Publications

• George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, Schmidt M, Spiegel C, Dealmeida N, Beaver KL, Borckardt JJ, Sun X, Jain S, Stein MB. A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014 May-Jun;7(3):421-31. doi: 10.1016/j.brs.2014.03.006. Epub 2014 Mar 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Anticipated): October 1, 2013

Study Registration Dates

• First Submitted: September 29, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 1, 2010

Study Record Updates

• Last Update Posted (Estimate): April 26, 2013
• Last Update Submitted That Met QC Criteria: April 24, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Suicidal ideation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Trauma and Stressor Related Disorders; Self-Injurious Behavior; Stress Disorders, Traumatic; Suicide; Brain Injuries; Stress Disorders, Post-Traumatic; Brain Injuries, Traumatic; Suicidal Ideation
• Other Study ID Numbers: INTRuST-TMS