Never Too Late: Safety and Efficacy of Deep TMS for Late-Life Depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-established treatment for major depressive disorder (MDD). Deep TMS utilizes specially designed H-Coils to stimulate the deep and broad cerebral regions associated with the reward system. The improved depth penetration of Deep TMS may be particularly important in late-life patients who often experience brain atrophy. The aim of this phase IV open-label study was to evaluate the safety and efficacy of Deep TMS in patients with late-life MDD. Data were collected from 247 patients with MDD aged 60-91 at 16 sites who had received at least 20 Deep TMS sessions for MDD. The outcome measures included self-assessment questionnaires (Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory-II (BDI-II)) and clinician-based scales (21-item Hamilton Depression Rating Scale (HDRS-21)). Following 30 sessions of Deep TMS, there was a 79.4% response and 60.3% remission rate on the most rated scale. The outcomes on the PHQ-9 were similar (76.6% response and 54.7% remission rate). The highest remission and response rates were observed with the HDRS physician-rated scale after 30 sessions (89% response and a 78% remission rate). After 20 sessions, there was a 73% response and 73% remission rate on the HDRS. Consistent with prior studies, the median onset of response was 14 sessions (20 days). The median onset of remission was 15 sessions (23 days). The treatment was well tolerated, with no reported serious adverse events. These high response and remission rates in patients with treatment-resistant late-life depression suggest that Deep TMS is a safe, well-tolerated and effective treatment for this expanded age range of older adults.

Deep TMS H1 Coil treatment for depression: Results from a large post marketing data analysis.

Phase IV study evaluated Deep TMS for major depression in community settings. Data were aggregated from 1753 patients at 21 sites, who received Deep TMS (high frequency or iTBS) using the H1 coil. Outcome measures varied across subjects and included clinician-based scales (HDRS-21) and self-assessment questionnaires (PHQ-9, BDI-II). 1351 patients were included in the analysis, 202 received iTBS. For participants with data from at least 1 scale, 30 sessions of Deep TMS led to 81.6% response and 65.3% remission rate. 20 sessions led to 73.6% response and 58.1% remission rate. iTBS led to 72.4% response and 69.2% remission. Remission rates were highest when assessed with HDRS (72%). In 84% of responders and 80% of remitters, response and remission was sustained in the subsequent assessment. Median number of sessions (days) for onset of sustained response was 16 (21 days) and for sustained remission 17 (23 days). Higher stimulation intensity was associated with superior clinical outcomes. This study shows that beyond its proven efficacy in RCTs, Deep TMS with the H1 coil is effective for treating depression under naturalistic conditions, and the onset of improvement is usually within 20 sessions. However, initial non-responders and non-remitters benefit from extended treatment.

Pursuing personalized medicine for depression by targeting the lateral or medial prefrontal cortex with Deep TMS.

BACKGROUNDMajor depressive disorder (MDD) can benefit from novel interventions and personalization. Deep transcranial magnetic stimulation (Deep TMS) targeting the lateral prefrontal cortex (LPFC) using the H1 coil was FDA cleared for treatment of MDD. However, recent preliminary data indicate that targeting the medial prefrontal cortex (MPFC) using the H7 coil might induce outcomes that are as good or even better. Here, we explored whether Deep TMS targeting the MPFC is noninferior to targeting the LPFC and whether electrophysiological or clinical markers for patient selection can be identified.METHODSThe present prospective, multicenter, randomized study enrolled 169 patients with MDD for whom antidepressants failed in the current episode. Patients were randomized to receive 24 Deep TMS sessions over 6 weeks, using either the H1 coil or the H7 coil. The primary efficacy endpoint was the change from baseline to week 6 in Hamilton Depression Rating Scale scores.RESULTSClinical efficacy and safety profiles were similar and not significantly different between groups, with response rates of 60.9% for the H1 coil and 64.2% for the H7 coil. Moreover, brain activity measured by EEG during the first treatment session correlated with clinical outcomes in a coil-specific manner, and a cluster of baseline clinical symptoms was found to potentially distinguish between patients who can benefit from each Deep TMS target.CONCLUSIONThis study provides a treatment option for MDD, using the H7 coil, and initial guidance to differentiate between patients likely to respond to LPFC versus MPFC stimulation targets, which require further validation studies.TRIAL REGISTRATIONClinicalTrials.gov NCT03012724.FUNDINGBrainsWay Ltd.

Real-world efficacy of deep TMS for obsessive-compulsive disorder: Post-marketing data collected from twenty-two clinical sites.

BACKGROUND: Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. METHODS: All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. RESULTS: Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. CONCLUSIONS: In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.

The Relationship between Trauma Exposure and Psychiatric Hospitalization for Suicide Ideation or Suicide Attempt among Patients Admitted to a Military Treatment Setting.

Suicide attempts and psychiatric hospitalization represent the final outcomes of a complex dynamical system of interacting factors that influence a particular individual's likelihood of engaging in suicidal behavior, as well as their ability to seek help prior to acting upon suicidal impulses. This study examined the association between different types of lifetime trauma exposure and the likelihood of psychiatric hospitalization following a suicide attempt (SA) rather than suicidal ideation (SI) alone. Electronic medical records for 1100 U.S. military service members and their dependents admitted to a military psychiatric inpatient setting for SA or SI were reviewed for documented lifetime trauma exposure history. Findings indicated that exposure to at least one childhood trauma of any type, and childhood neglect in particular, increased the likelihood that an individual would be hospitalized for SA rather than SI. Exploratory gender-stratified analyses demonstrated that childhood neglect, childhood sexual abuse, and adulthood traumatic loss may be linked with the likelihood of being hospitalized for SA. These findings demonstrate the importance of developing more detailed and nuanced conception of factors known to be associated with suicide as their effects may depend on details of their timing and nature, as well as their interactions with other systems.

Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions.

Background: Since 2000, over 413,000 US service members (SM) experienced at least one traumatic brain injury (TBI), and 40% of those with in-theater TBIs later screened positive for comorbid psychological health (PH) conditions, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many SMs with these persistent symptoms fail to achieve a recovery that results in a desirable quality of life or return to full duty. Limited information exists though to guide treatment for SMs with a history of mild TBI (mTBI) and comorbid PH conditions. This report presents the methods and outcomes of an interdisciplinary intensive outpatient program (IOP) in the treatment of SMs with combat-related mTBI and PH comorbidities. The IOP combines conventional rehabilitation therapies and integrative medicine techniques with the goal of reducing morbidity in multiple neurological and behavioral health domains and enhancing military readiness. Methods: SMs (n = 1,456) with residual symptoms from mTBI and comorbid PH conditions were treated in a 4-week IOP at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC). The IOP uses an interdisciplinary, holistic, and patient-centric rehabilitative care model. Interdisciplinary teams provide a diagnostic workup of neurological, psychiatric, and existential injuries, and from these assessments, individualized care plans are developed. Treatment response was assessed using the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Satisfaction With Life Scale (SWLS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Epworth Sleepiness Scale (ESS), and Headache Impact Test-6 (HIT-6) and administered at admission, discharge, and at 1, 3, and 6 months post-discharge. Findings: Following treatment in the IOP, the symptomatic patients had statistically significant and clinically meaningful improvements across all outcome measures. The largest effect size was seen with GAD-7 (r = 0.59), followed by PHQ-8 (r = 0.56), NSI (r = 0.55), PCL-M (r = 0.52), ESS (r = 0.50), SWLS (r = 0.49), and HIT-6 (r = 0.42). In cross-sectional follow ups, the significant improvements were sustained at 1, 3, and 6 months post-discharge. Interpretation: This report demonstrates that an interdisciplinary IOP achieves significant and sustainable symptom recovery in SMs with combat-related mTBI and comorbid PH conditions and supports the further study of this model of care in complex medical conditions.

Inpatient psychiatric care following a suicide-related hospitalization: A pilot trial of Post-Admission Cognitive Therapy in a military medical center.

OBJECTIVE: Individuals with a recent suicidal crisis are typically admitted for inpatient psychiatric care. However, targeted inpatient interventions for suicide prevention remain sparse. Thus, this pilot randomized controlled trial evaluated a brief inpatient cognitive behavioral protocol, Post-Admission Cognitive Therapy (PACT) for the prevention of suicide. METHODS: United States service members and beneficiaries (N = 24) psychiatrically hospitalized at a military medical center due to a recent suicidal crisis were randomized to receive either PACT plus Enhanced Usual Care (PACT + EUC) or EUC alone. Blinded follow-up assessments were conducted at one-, two-, and three-months post discharge. The degree of change and variability of response to PACT for repeat suicide attempt(s) (primary outcome), as well as depression, hopelessness, and suicide ideation (secondary outcomes) were examined. RESULTS: Significant between-group differences in re-attempt status were not found. Reliable Change Index analyses indicated that among the most clinically severe participants, a greater proportion of PACT + EUC participants compared with EUC participants met criteria for clinically significant reductions on depression (40% versus 25%), hopelessness (67% versus 50%), suicide ideation (45% versus 33%), and posttraumatic stress symptomatology (40% versus 25%). CONCLUSIONS: PACT is a promising inpatient cognitive behavioral intervention for suicide risk reduction. The efficacy of PACT is currently being evaluated in a well-powered multi-site randomized controlled trial.

Demographic and Clinical Characteristics of Military Service Members Hospitalized Following a Suicide Attempt versus Suicide Ideation.

Psychiatric hospitalization for a suicide attempt (SA), rather than suicide ideation (SI) alone, is a stronger risk indicator for eventual suicide death. Yet, little is known about demographic and clinical characteristics differentiating those admitted for SA versus SI. Understanding these differences has implications for assessment and treatment. A retrospective review of electronic medical records (EMRs) was performed on service members (n = 955) admitted for SA or SI at the Walter Reed Army Medical Center between 2001-2006. Service members hospitalized for SA were younger compared to those hospitalized for SI. The proportion of women admitted for SA was significantly higher than those admitted for SI whereas their male counterparts showed the opposite pattern. Patients admitted for SA, versus SI, had significantly higher prevalence of adjustment disorder with mixed disturbance of emotion and conduct (MDEC), personality disorder not otherwise specified (PDNOS), and borderline personality disorder (BPD). Patients admitted for SI had significantly higher prevalence of adjustment disorder with depressed mood and deferred Axis II diagnosis, compared to those admitted for SA. There were no significant between-group differences in the average or median number of documented prior suicide attempts. Findings highlight the need for more standardized assessment, diagnostic decision-making, and documentation practices for all patients.

Pilot trial of post-admission cognitive therapy: Inpatient program for suicide prevention.

Suicide remains a significant public health problem for the United States military. Trauma-related diagnoses such as acute stress disorder (ASD) or posttraumatic stress disorder (PTSD) may exacerbate suicide risk, particularly among service members psychiatrically hospitalized following suicide-related events. To date, treatments to address suicide risk and trauma symptomatology among service members within inpatient milieus have been nonexistent. To address this gap, a randomized controlled pilot trial of Post-Admission Cognitive Therapy (PACT) was conducted to evaluate a targeted cognitive-behavioral program among traumatized military personnel (N = 36) hospitalized following a recent suicide attempt. All participants met criteria for ASD or PTSD and were randomly assigned to receive either PACT and enhanced usual care (PACT + EUC) or EUC alone. PACT consisted of six 60- to 90-min individual psychotherapy sessions, adapted from Brown et al.'s (2005) cognitive therapy protocol for suicide prevention. Blinded follow-up assessments were conducted at 1-, 2-, and 3-months postpsychiatric discharge. The primary outcome was days until repeat suicide attempt. Secondary outcomes included depression, hopelessness, suicide ideation, and PTSD symptoms. Participants did not significantly differ in reattempt status. However, based on reliable change index analyses, a greater proportion of PACT + EUC versus EUC participants met criteria for clinically significant change on measures of depression (100% vs. 78%), hopelessness (83% vs. 57%), and PTSD symptom severity (100% vs. 38%), but not for suicide ideation (60% vs. 67%). PACT is an innovative inpatient protocol, currently under evaluation in a well-powered multisite RCT for its efficacy in reducing subsequent suicidal behaviors. (PsycINFO Database Record

Motor impulsivity differentiates between psychiatric inpatients with multiple versus single lifetime suicide attempts.

A history of multiple suicide attempts conveys greater risk for suicide than a single attempt. Impulsivity may partially explain the association between multiple attempts and increased risk. We examined trait impulsivity, ability to engage in goal-directed behaviors, and impulse control among psychiatrically hospitalized United States military personnel and their dependents. Individuals with a history of multiple versus single attempts had significantly higher motor impulsivity, indicating spur of the moment action. Providers are encouraged to directly assess and treat motor impulsivity among suicidal individuals. Further research should explore whether motor impulsivity is a mechanism of change in psychosocial suicide prevention interventions.

Evaluating the clinical utility of the Validity-10 for detecting amplified symptom reporting for patients with mild traumatic brain injury and comorbid psychological health conditions.

The objective of this study was to compare the Validity-10 scale with the PAI Negative Impression Management Scale (PAI-NIM) for detecting exaggerated symptom reporting in active-duty military service members (SMs) admitted with unremitting mild TBI symptoms and comorbid psychological health conditions (mTBI/PH). Data were analyzed from 254 SMs who completed the Neurobehavioral Symptom Inventory (NSI) and Personality Assessment Inventory (PAI) as a part of a larger battery of self-report symptom scales upon admission to the intensive-outpatient TBI treatment program at a military medical center. Symptom exaggeration was operationalized using the PAI Negative Impression Management Scale (PAI-NIM). A PAI-NIM score of ≥73 was categorized as positive for symptom exaggeration (SVTpos), while a lower score was categorized as negative for symptom exaggeration (SVTneg). SMs in the SVTpos group (n = 34) had significantly higher scores (p ≤ .004) on the PAI clinical scales as well as on the NSI total score (range: d = 0.59-1.91) compared to those who were SVTneg (n = 220). The optimal cut-score for the NSI Val-10 scale to identify possible symptom exaggeration was ≥26 (sensitivity = .29, specificity = .95, PPP = .74, NPP = .71). In patients suffering from mTBI/PH, the Validity-10 requires a higher cut-score than previously reported to be useful as a metric of exaggerated symptom reporting.

The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder.

BACKGROUND: Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4-6 weeks (20-30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013. METHODS: This consensus review was written by cTMSs leaders, informed by membership polls, and approved by the governing board. It summarizes current evidence for the safety and efficacy of the use of TMS therapy for treating depression in routine clinical practice. Authors systematically reviewed the published TMS antidepressant therapy clinical trials. Studies were then assessed and graded on their strength of evidence using the Levels of Evidence framework published by the University of Oxford Centre for Evidence Based Medicine. The authors then summarize essentials for using TMS therapy in routine clinical practice settings derived from discussions and polls of cTMSs members. Finally, each summary clinical recommendation is presented with the substantiating peer-reviewed, published evidence supporting that recommendation. When the current published clinical trial evidence was insufficient or incomplete, expert opinion was included when sufficient consensus was available from experienced clinician users among the membership of the cTMSs, who were polled at the Annual Meetings in 2014 and 2015. CONCLUSIONS: Daily left prefrontal TMS has substantial evidence of efficacy and safety for treating the acute phase of depression in patients who are treatment resistant or intolerant. Following the clinical recommendations in this document should result in continued safe and effective use of this exciting new treatment modality.

Three Scoring Approaches to the Neurobehavioral Symptom Inventory for Measuring Clinical Change in Service Members Receiving Intensive Treatment for Combat-Related mTBI.

OBJECTIVE: To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. SETTING: A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. PARTICIPANTS: Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. DESIGN: Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. MAIN MEASURES: Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). RESULTS: All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. CONCLUSION: Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.

Severity of Depression Predicts Remission Rates Using Transcranial Magnetic Stimulation.

BACKGROUND: Multiple factors likely impact response and remission rates in the treatment of depression with repetitive transcranial magnetic stimulation (rTMS). Notably, the role of symptom severity in outcomes with rTMS is poorly understood. OBJECTIVE/HYPOTHESIS: This study investigated the predictors of achieving remission in patients suffering from depression who receive ≥3 rTMS treatments per week. METHODS: Available data on 41 patients treated at Walter Reed National Military Medical Center from 2009 to 2014 were included for analysis. Patients received a range of pulse sequences from 3,000 to 5,000 with left-sided or bilateral coil placement. Primary outcome measures were total score on the Patient Health Questionnaire-9 or the Quick Inventory of Depressive Symptomatology-Self Rated. Remission was defined as a total score less than five, and response was defined as a 50% decrease in the total score on both outcome metrics. Outcomes in patients diagnosed as suffering from mild or moderate depression were compared to those suffering from severe depression. RESULTS: Of the 41 patients receiving treatment, 16 reached remission and 18 reached response by the end of treatment. Remission rate was associated with the initial severity of depression, with patients with mild or moderate depression reaching remission at a significantly higher rate than those with severe depression. Total number of rTMS sessions or length of treatment was not predictors of remission. CONCLUSION: Patients with a baseline level of depression characterized as mild or moderate had significantly better outcomes following rTMS compared to patients with severe depression.

A Review of Transcranial Magnetic Stimulation as a Treatment for Post-Traumatic Stress Disorder.

Patients with post-traumatic stress disorder (PTSD) may fail to achieve adequate relief despite treatment with psychotherapy, pharmacotherapy, or complementary medicine treatments. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation procedure that can alter neuronal activity through administration of various pulse sequences and frequencies. TMS may theoretically have promise in correcting alterations observed in patients with PTSD. While the precise treatment location and pulse sequences remain undefined, current evidence suggests two promising targets, the right dorsolateral prefrontal cortex and the medial prefrontal cortex. The beneficial effects may be due to the secondary or indirect regulation of other brain structures that may be involved in the mood regulatory network. TMS may be an effective part of a comprehensive treatment program for PTSD, although significant work remains to define optimal treatment parameters and clarify how it fits within a broader traditional treatment program.

Significant reduction in phantom limb pain after low-frequency repetitive transcranial magnetic stimulation to the primary sensory cortex.

OBJECTIVE: Phantom limb pain (PLP) is believed to be linked to the reorganization of the deafferented sensory cortex. We present a case of a patient with upper extremity PLP who was successfully treated with repetitive transcranial magnetic stimulation (rTMS). METHODS: We treated an active duty service member who suffered an amputation of his right upper extremity after sustaining a blast injury in Afghanistan. He had 28 sessions of alternating sequences of rTMS to the left dorsolateral prefrontal cortex and primary sensory cortex of the left cerebral hemisphere. Pain intensity was assessed with the Visual Analogue Scale. RESULTS: We delivered 1 Hz stimulation to the sensory cortex corresponding to the area of amputation five times a week. After 4 sessions, the patient's pain decreased from a Visual Analogue Scale of 5 to 2. Left 10 Hz stimulation was added and after 28 sessions, the pain decreased from 2 to 1. CONCLUSIONS: Our findings support that rTMS was an effective modality for this patient in treating his PLP. The significance of 10 Hz stimulation is unknown because of the lack of an effect size and is possibly associated with a floor effect.

Transcranial magnetic stimulation as an antidepressant alternative in a patient with Brugada syndrome and recurrent syncope.

Brugada syndrome (BrS) is a common occult cause of sudden cardiac arrest in otherwise healthy-appearing adults. The pathognomonic electrocardiographic pattern may be unmasked only by certain medications, many of which are unknown. We report a case of a depressed but otherwise healthy man with an asymptomatic right bundle branch block on electrocardiography who experienced antidepressant-induced BrS and ultimately recovered with transcranial magnetic stimulation (TMS). After an initial trial of nortriptyline, the patient's depressive symptoms improved; however, he experienced a syncopal event and was subsequently diagnosed as having BrS. Cross titration to bupropion, which had not previously been known to exacerbate BrS, was followed by another cardiac event. As a result, the patient was referred for TMS as a substitute for pharmacotherapy. After 31 TMS sessions over 8 weeks, the patient demonstrated significant improvement by subjective report and objective reduction in his Patient Health Questionnaire-9 scores from 10 (moderate) to 1 (minimal). Transcranial magnetic stimulation is a Food and Drug Administration-approved nonpharmacologic treatment for depression. Given the potential lethality of BrS with known and unknown psychopharmacologic agents, providers should consider TMS as first-line therapy in this patient population. Bupropion should be added to the list of agents known to exacerbate this disease.

Safety Planning for Military (SAFE MIL): rationale, design, and safety considerations of a randomized controlled trial to reduce suicide risk among psychiatric inpatients.

Mental health related hospitalizations and suicide are both significant public health problems within the United States Department of Defense (DoD). To date, few evidence-based suicide prevention programs have been developed for delivery to military personnel and family members admitted for psychiatric inpatient care due to suicidal self-directed violence. This paper describes the rationale and detailed methodology for a study called Safety Planning for Military (SAFE MIL) which involves a randomized controlled trial (RCT) at the largest military treatment facility in the United States. The purpose of this study is to test the efficacy of a brief, readily accessible, and personalized treatment called the Safety Planning Intervention (Stanley and Brown, 2012). Primary outcomes, measured by blinded assessors at one and six months following psychiatric discharge, include suicide ideation, suicide-related coping, and attitudes toward help seeking. Additionally, given the study's focus on a highly vulnerable patient population, a description of safety considerations for human subjects' participation is provided. Based on this research team's experience, the implementation of an infrastructure in support of RCT research within DoD settings and the processing of regulatory approvals for a clinical trial with high risk suicidal patients are expected to take up to 18-24 months. Recommendations for expediting the advancement of clinical trials research within the DoD are provided in order to maximize cost efficacy and minimize the research to practice gap.

A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients.

BACKGROUND: Suicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4-6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality. DESIGN: This study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD). PATIENTS: Research staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both. TMS METHODS: Repetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation. MAIN OUTCOME MEASURE: Primary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations. RESULTS: This intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change -15.3 points, active change -15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change -6.4 points, active -10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change -5.9 (95% CI: -10.1, -1.7), active -13 points (95% CI: -18.7, -7.4); P = 0.054]. Subjective ratings of 'being bothered by thoughts of suicide' declined non-significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change -31.9 (95% CI: -41.7, -22.0), active change -42.5 (95% CI: -53.8, -31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change -24.9 (95% CI: -34.4, -15.3), active change -43.8 (95% CI: -57.2, -30.3); P = 0.028]. CONCLUSIONS: Delivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.

Diagnostic and psychosocial differences in psychiatrically hospitalized military service members with single versus multiple suicide attempts.

INTRODUCTION: Individuals with multiple versus single suicide attempts present a more severe clinical picture and may be at greater risk for suicide. Yet group differences within military samples have been vastly understudied. PURPOSE: The objective is to determine demographic, diagnostic, and psychosocial differences, based on suicide attempt status, among military inpatients admitted for suicide-related events. METHOD: A retrospective chart review design was used with a total of 423 randomly selected medical records of psychiatric admissions to a military hospital from 2001 to 2006. RESULTS: Chi-square analyses indicated that individuals with multiple versus single suicide attempts were significantly more likely to have documented childhood sexual abuse (p =.025); problem substance use (p=.001); mood disorder diagnosis (p=.005); substance disorder diagnosis (p =.050); personality disorder not otherwise specified diagnosis (p =.018); and Axis II traits or diagnosis (p=.038) when compared to those with a single attempt history. Logistic regression analyses showed that males with multiple suicide attempts were more likely to have problem substance use (p=.005) and a mood disorder diagnosis (p =.002), while females with a multiple attempt history were more likely to have a history of childhood sexual (p =.027). DISCUSSION: Clinically meaningful differences among military inpatients with single versus multiple suicide attempts exist. Targeted Department of Defense suicide prevention and intervention efforts that address the unique needs of these two specific at-risk subgroups are additionally needed.