Diffuse optical tomography for mapping cerebral hemodynamics and functional connectivity in delirium.

INTRODUCTION: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities. METHODS: Twenty-five delirious and matched non-delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium. RESULTS: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls. DISCUSSION: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias. HIGHLIGHTS: We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

Predictive modeling of initiation and delayed mental health contact for depression.

BACKGROUND: Depression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment. METHODS: We obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis. RESULTS: 108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586-0.602; machine learning F-measure = 0.46). CONCLUSIONS: Having VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.

Mental health treatment utilization patterns among 108,457 Afghanistan and Iraq veterans with depression.

People with depression often underutilize mental health care. This study was conceived as a first step toward a clinical decision support tool that helps identify patients who are at higher risk of underutilizing care. The primary goals were to (a) describe treatment utilization patterns, early termination, and return to care; (b) identify factors associated with early termination of treatment; and (c) evaluate the accuracy of regression models to predict early termination. These goals were evaluated in a retrospective cohort analysis of 108,457 U.S. veterans who received care from the Veterans Health Administration between 2001 and 2021. Our final sample was 16.5% female with an average age of 34.5. Veterans were included if they had a depression diagnosis, a positive depression screen, and received general health care services at least a year before and after their depression diagnosis. Using treatment quality guidelines, the threshold for treatment underutilization was defined as receiving fewer than four psychotherapy sessions or less than 84 days of antidepressants. Over one fifth of veterans (21.6%) received less than the minimally recommended care for depression. The odds of underutilizing treatment increased with lack of Veterans Administration benefits, male gender, racial/ethnic minority status, and having received mental health treatment in the past (adjusted OR > 1.1). Posttraumatic stress disorder comorbidity correlated with increased depression treatment utilization (adjusted OR < .9). Models with demographic and clinical information from medical records performed modestly in classifying patients who underutilized depression treatment (area under the curve = 0.595, 95% CI [0.588, 0.603]). Most veterans in this cohort received at least the minimum recommended treatment for depression. To improve the prediction of underutilization, patient factors associated with treatment underutilization likely need to be supplemented by additional clinical information. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effectiveness of Prefrontal Transcranial Magnetic Stimulation for Depression in Older US Military Veterans.

OBJECTIVE: While typical aging is associated with decreased cortical volume, major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) likely exacerbates this process. Cerebral atrophy leads to increased coil-to-cortex distance and when using transcranial magnetic stimulation (TMS), potentially reducing effectiveness in older adults. METHODS: Data from a large-scale quality improvement project was used. Included veterans eligible for TMS and completed TMS treatment. Age was assessed as a predictive factor of depression outcomes after TMS treatment among veterans. Secondary analyses examined the impact of age on 1) MDD response and remission and 2) MDD change within MDD-only verses comorbid MDD and PTSD groups. RESULTS: The entire sample included 471 veterans. Primary analysis revealed age as a negative predictor of depression outcomes (p = 0.019). Secondary analyses found age to be a significant predictor of remission (p = 0.004), but not clinical response. Age was not a predictive factor in depression outcomes between those with MDD-only compared to MDD+PTSD. CONCLUSIONS: Increased age predicts greater MDD symptom reduction after TMS. Although age did not predict response rates, it did predict increased rates of remission in veterans. Age did not differentially predict depression outcomes between those with or without PTSD. The sample size was sufficient to discern a difference in efficaciousness, and limitations were those inherent to registry studies in veterans. This data indicates that TMS can be an important treatment option for older individuals.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment.

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.S. veterans diagnosed with combat-related PTSD were randomized to receive either active or sham repetitive transcranial magnetic stimulation (rTMS). All received cognitive processing therapy, CPT+A, which requires a written account of the index trauma. They were tested before and 6 months after protocol completion. P3a amplitude and response time decreases were driven largely by the changes in the responses to the trauma-related stimuli, and this decrease correlated to the decrease in PTSD symptoms. The amplitude changes were greater in those who received rTMS + CPT than in those who received sham rTMS + CPT, suggesting that rTMS plays beneficial role in reducing arousal and threat bias, which may allow for more effective engagement in trauma-focused PTSD treatment.

An accelerated course of TMS using intermittent theta burst for veterans with major depressive disorder: A case series.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a neuro-modulation technique for treatment-resistant major depressive disorder (MDD). Standard TMS protocols for MDD involve once-daily treatment for 6 to 9 weeks. We report a case series of an accelerated TMS protocol for outpatient MDD treatment. METHODS: From July 2020 through January 2021, patients deemed appropriate candidates for TMS treatment were offered an accelerated TMS protocol consisting of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex, localized by the Beam F3 method, and consisting of 5 treatments daily for 5 days. Assessment scales were obtained as part of standard clinical care. RESULTS: A total of 19 veterans received the accelerated protocol and 17 completed treatment. Statistically significant mean reductions from baseline to end of treatment were observed across all assessment scales. Remission and response rates, as defined by changes in Montgomery-Åsberg Depression Rating Scale scores, were 47.1% and 64.7%, respectively. Treatments were well tolerated without unexpected or serious adverse events. CONCLUSIONS: This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days. Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium.

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder.

Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD), however, the evidence in veterans has been mixed. To this end, VA implemented a nationwide TMS program that included evaluating clinical outcomes within a naturalistic design. TMS was hypothesized to be safe and provide clinically meaningful reductions in MDD and posttraumatic stress disorder (PTSD) symptoms. METHODS: Inclusion criteria were MDD diagnosis and standard clinical TMS eligibility. Of the 770 patients enrolled between October 2017 and March 2020, 68.4% (n = 521) met threshold-level PTSD symptom criteria. Treatments generally used standard parameters (e.g., left dorsolateral prefrontal cortex, 120% motor threshold, 10 Hz, 3000 pulses/treatment). Adequate dose was operationally defined as 30 sessions. MDD and PTSD symptoms were measured using the 9-item patient health questionnaire (PHQ-9) and PTSD checklist for DSM-5 (PCL-5), respectively. RESULTS: Of the 770 who received at least one session, TMS was associated with clinically meaningful (Cohen's d>1.0) and statistically significant (all p<.001) reductions in MDD and PTSD. Of the 340 veterans who received an adequate dose, MDD response and remission rates were 41.4% and 20%, respectively. In veterans with comorbid PTSD, 65.3% demonstrated clinically meaningful reduction and 46.1% no longer met PTSD threshold criteria after TMS. Side effects were consistent with the known safety profile of TMS. LIMITATIONS: Include those inherent to retrospective observational cohort study in Veterans. CONCLUSIONS: These multisite, large-scale data supports the effectiveness and safety of TMS for veterans with MDD and PTSD using standard clinical approaches.

Systematic review of preservation TMS that includes continuation, maintenance, relapse-prevention, and rescue TMS.

BACKGROUND: A dearth of evidence-based information exists to guide the delivery of transcranial magnetic stimulation (TMS) after a successful acute course of treatment for Major Depressive Disorder. METHODS: To provide guidance for clinicians, existing literature focused on "preservation TMS" was systematically reviewed and synthesized. Preservation TMS was defined as TMS used to sustain a clinical response after a successful acute course of treatment and included reports using the terms maintenance, continuation, relapse prevention, or rescue TMS. The review protocol was registered on Open Science Framework and reported following PRISMA guidelines. Data were abstracted by two authors and discrepancies were resolved by a third author. Primary outcome measures focused on clinical efficacy. The evaluated studies were graded using the Levels of Evidence criteria published by the Oxford Centre for Evidence-Based Medicine. RESULTS: The search included 536 abstracts and 16 additional papers, from which 63 full articles were screened. Data were abstracted from 30 qualifying sources (N=1,494) including 4 randomized controlled trials (one sham controlled), 14 open trials, and 12 case series. Overall, the quality of existing literature was low regarding efficacy but provided clear support for effectiveness and safety across a range of preservation TMS protocols based on mostly uncontrolled studies. CONCLUSIONS: Existing literature suggests that preservation TMS protocols significantly vary and are mostly supported by open trials and case series. Due to a lack of effective alternatives, preservation TMS will likely be required for certain patients who respond to acute TMS therapy. More studies of preservation TMS are critically needed.

Auditory N2 Correlates of Treatment Response in Posttraumatic Stress Disorder.

Emotional processing and cognitive control are implicated as being dysfunctional in posttraumatic stress disorder (PTSD) and targeted in cognitive processing therapy (CPT), a trauma-focused treatment for PTSD. The N2 event-related potential has been interpreted in the context of emotional processing and cognitive control. In this analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the N2 in responses to task-relevant target tones and task-irrelevant distractor sounds (e.g., a trauma-related gunshot and a trauma-unrelated lion's roar) and the associations between these responses and PTSD symptom changes. United States military veterans (N = 60) diagnosed with combat-related PTSD were randomized to either active or sham repetitive transcranial magnetic stimulation (rTMS) and received a CPT intervention that included a written trauma account element (CPT+A). Participants were tested before and 6 months after protocol completion. Reduction in N2 amplitude to the gunshot stimulus was correlated with reductions in reexperiencing, |r| = .445, and hyperarousal measures, |r| = .364. In addition, in both groups, the latency of the N2 event-related potential to the distractors became longer with treatment and the N2 latency to the task-relevant stimulus became shorter, ηp 2  = .064, both of which are consistent with improved cognitive control. There were no between-group differences in N2 amplitude and latency. Normalized N2 latencies, reduced N2 amplitude to threatening distractors, and the correlation between N2 amplitude reduction and PTSD symptom reduction reflect improved cognitive control, consistent with the CPT+A objective of addressing patients' abilities to respond more appropriately to trauma triggers.

Neuromodulation as an Augmenting Strategy for Behavioral Therapies for Anxiety and PTSD: a Narrative Review.

Purpose of Review: Post-traumatic stress disorder (PTSD) is a prevalent problem. Despite current treatments, symptoms may persist, and neuromodulation therapies show great potential. A growing body of research suggests that transcranial magnetic stimulation (TMS) is effective as a standalone treatment for PTSD, with recent research demonstrating promising use when combined synergistically with behavioral treatments. In this review, we survey this literature including data suggesting mechanisms involved in anxiety and PTSD that may be targeted by neurostimulation. Recent Findings: Evidence suggests the mechanism of action for TMS that contributes to behavioral change may be enhanced neural plasticity via increased functionality of prefrontal and subcortical/limbic structures and associated networks. Some research has demonstrated a behavioral change in PTSD and anxiety due to enhanced extinction learning or improved ability to think flexibly and reduce ruminative tendencies. Growing evidence suggests TMS may be best used as a therapeutic adjunct, at least acutely, for extinction-based exposure therapies in patients by accelerating therapy response. Summary: While TMS has shown promise as a standalone intervention, augmentation with psychotherapy is one avenue of interest. Non-responders to current EBPs might particularly benefit from this sort of targeted approach, and it may shorten treatment length, which would help the successful completion of a course of therapy.

Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18-70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.

Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression.

BACKGROUND: Although repetitive transcranial magnetic stimulation ('TMS') is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran's Health Administration. METHODS: Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at 'baseline' pre-TMS commencement, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. DISCUSSION: To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663481 , December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

The Relationship of Transcranial Magnetic Stimulation With Sleep and Plasticity.

Neuroplasticity is an area of expanding interest in psychiatry. Plasticity and metaplasticity are processes contributing to the scaling up and down of neuronal connections, and they are involved with changes in learning, memory, mood, and sleep. Effective mood treatments, including repetitive transcranial magnetic stimulation (rTMS), are reputed to work via changes in neuronal circuitry. This article explores the interrelatedness of sleep, plasticity, and rTMS treatment. A PubMed-based literature review was conducted to identify all available studies examining the relationship of rTMS, plasticity, and sleep. Key words used in this search included "TMS," "transcranial magnetic stimulation," "plasticity," "metaplasticity," "sleep," and "insomnia." Depressed mood tends to be associated with impaired neural plasticity, while antidepressant treatments can augment neural plasticity. rTMS impacts plasticity, yielding long-lasting effects, with differing impacts on the waking and sleeping brain. Higher quality sleep promotes plasticity and learning. Reports on the sleep impact of high-frequency and low-frequency rTMS are mixed. The efficacy of rTMS may rely on brain plasticity manipulation, enhanced via the stimulation of neural circuits. Total sleep time and sleep continuity are sleep qualities that are likely necessary but insufficient for the homeostatic plasticity driven by slow-wave sleep. Understanding the relationship between sleep and rTMS treatment is likely critical to enhancing outcomes.

Impact of Comorbid PTSD on Outcome of Repetitive Transcranial Magnetic Stimulation (TMS) for Veterans With Depression.

OBJECTIVE: A recent randomized controlled trial of repetitive transcranial magnetic stimulation (TMS) for major depressive disorder (MDD) in veterans raised the question of whether comorbid posttraumatic stress disorder (PTSD) negatively impacted the outcome of TMS in veterans. To address this, a quality database was analyzed to compare outcomes of MDD treated with TMS in veterans with and without comorbid PTSD. METHODS: The clinical outcomes of all consecutive veterans with MDD treated with TMS at the James A. Haley Veterans' Hospital as outpatients from October 2013 through September 2018 were included. Patients were initially evaluated by an experienced psychiatrist, and the diagnosis of MDD was made by clinical evaluation per DSM-IV-TR/DSM-5 criteria. At the start of treatment, after every 5 treatments, and at the end of treatment, patients were assessed with self-report and clinician-rated scales of depression. All data were abstracted from an existing quality database. RESULTS: Among the 118 patients treated with TMS for depression, 55 (47%) had comorbid PTSD and 63 (53%) had no comorbid PTSD. Response and remission rates by score on the Montgomery-Asberg Depression Rating Scale were similar between patients with PTSD (52.5% and 40.9%, respectively) and without PTSD (53.8% and 35.6%, respectively). No seizures or persistent adverse effects were observed or reported in either group. CONCLUSIONS: Comorbid PTSD did not impact the outcome of TMS for depression in this sample of veterans. Future studies should include formal ratings of PTSD to determine if the severity of PTSD affects the outcome.

A Clinical Program to Implement Repetitive Transcranial Magnetic Stimulation for Depression in the Department of Veterans Affairs.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) uses a device to create magnetic fields that cause electrical current to flow into targeted neurons in the brain. The most common clinical use of rTMS is for the treatment of major depressive disorder (MDD). The annual suicide rate of veterans has been higher than the national average; treating depression with rTMS would likely decrease suicide risk. MDD in many patients can be chronic and reoccurring with medication and psychotherapy providing inadequate relief. METHODS: A pilot program was created to supply rTMS devices to 35 different sites in the VA nationwide in order to treat treatment-resistant depression. CONCLUSIONS: At time of analysis more than 950 veterans have started the program and 412 have finished. Nationwide, we have seen the depression scores decline, indicating an improvement in well-being. In addition, there is high patient satisfaction. Collecting data on a national level is a powerful way to examine rTMS efficacy and predictors of response which might be lost on a smaller subset of cases.