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Cilli SL, Goldberg MA, Cosmo C, Arulpragasam AR, Zand Vakili A, Berlow YA, Philip NS. Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Generalized Anxiety Disorder. Curr Top Behav Neurosci 2024. [PMID: 39505816 DOI: 10.1007/7854_2024_540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024]
Abstract
Posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD) are debilitating psychiatric disorders. While treatments are often effective, many patients do not adequately respond or experience significant side effects. Transcranial magnetic stimulation (TMS) is an emerging approach for treating PTSD and GAD. Several randomized clinical trials have demonstrated that TMS over the dorsolateral prefrontal cortex may be efficacious in reducing psychiatric symptoms; however, results are inconsistent regarding whether any parameter or treatment paradigm is superior. Other RCTs have targeted novel brain regions using newer TMS modalities. Combining TMS with psychotherapy may augment response in patients with PTSD, yet results are inconclusive. Little research has been done on TMS in combination with psychotherapy for GAD, indicating a need for further investigation. Future studies may assess TMS parameter optimization for enhancing effectiveness and improving therapeutic response duration. Identifying response biomarkers through functional magnetic resonance imaging and electroencephalography may offer a means to predict and monitor clinical response as precision methods to improve treatment response.
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Affiliation(s)
- Samantha L Cilli
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Miriam A Goldberg
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Camila Cosmo
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Amanda R Arulpragasam
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Amin Zand Vakili
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Yosef A Berlow
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S Philip
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA.
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
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Jiang C, Yang Y, Wu L, Liu W, Zhao G. Low-frequency repetitive transcranial magnetic stimulation for the treatment of post-traumatic stress disorder and its comparison with high-frequency stimulation: a systematic review and meta-analysis. Ther Adv Psychopharmacol 2024; 14:20451253241271870. [PMID: 39411406 PMCID: PMC11475085 DOI: 10.1177/20451253241271870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 06/24/2024] [Indexed: 10/19/2024] Open
Abstract
Background Repetitive transcranial magnetic stimulation (rTMS) showed potentially beneficial effects for the treatment of post-traumatic stress disorder (PTSD). Low-frequency (LF) rTMS decreases neuronal excitability and may have better safety compared to high-frequency (HF) rTMS. However, there lacks meta-analysis specifically focusing on LF rTMS. Objectives To specifically explore the efficacy and safety of LF rTMS for treating PTSD. Methods Databases including PubMed, EMBASE, MEDLINE, and Web of Science were systematically searched from inception to October 17, 2023. Both randomized controlled trials (RCTs) and open trials of LF rTMS on PTSD were included, and we additionally included RCTs comparing HF rTMS and sham treatment on PTSD. First, we qualitatively summarized parameters of LF rTMS treatment; then, we extracted data from the LF rTMS treatment subgroups of these studies to examine its effect size and potential influencing factors; third, we compared the effect sizes among LF rTMS, HF rTMS and sham treatment through network meta-analysis of RCTs. Results In all, 15 studies with a sample size of 542 participants were included. The overall effect size for LF rTMS as a treatment for PTSD was found as Hedges' g = 1.02 (95% CI (0.56, 1.47)). Meta-regression analysis did not reveal any influencing factors. Network meta-analysis showed that compared to sham treatment, only HF rTMS on the right dorsolateral prefrontal cortex (DLPFC) demonstrated a significant advantage in ameliorating PTSD symptoms, while LF rTMS on the right DLPFC showed a trend toward advantage, but the difference was not significant. Conclusion The current literature shows LF rTMS has effect in treating PTSD caused by various traumatic events. However, present limited number of RCT studies only showed LF rTMS to have a trend of advantage compared to sham treatment in treating PTSD caused by external traumatic events. In the future, more RCTs are needed to be made to confirm the efficacy of LF rTMS. Additionally, studies are required to elucidate the underlying mechanism in order to further improve its efficacy in different traumatic populations. PROSPERO registration number CRD42023470169.
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Affiliation(s)
- Che Jiang
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA Guangzhou City, Guangdong Province, China
| | - Yong Yang
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, Henan Province, China
| | - Lili Wu
- Lab for Post-traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, China
| | - Weizhi Liu
- Lab for Post-traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, 800 Xiangyin Road, Shanghai 200433, China
| | - Gang Zhao
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA Guangzhou City, Guangdong Province 510010, China
- First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong Province 510515, China
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Brown R, Cherian K, Jones K, Wickham R, Gomez R, Sahlem G. Repetitive transcranial magnetic stimulation for post-traumatic stress disorder in adults. Cochrane Database Syst Rev 2024; 8:CD015040. [PMID: 39092744 PMCID: PMC11295260 DOI: 10.1002/14651858.cd015040.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
BACKGROUND The estimated lifetime prevalence of post-traumatic stress disorder (PTSD) in adults worldwide has been estimated at 3.9%. PTSD appears to contribute to alterations in neuronal network connectivity patterns. Current pharmacological and psychotherapeutic treatments for PTSD are associated with inadequate symptom improvement and high dropout rates. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive therapy involving induction of electrical currents in cortical brain tissue, may be an important treatment option for PTSD to improve remission rates and for people who cannot tolerate existing treatments. OBJECTIVES To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on post-traumatic stress disorder (PTSD) in adults. SEARCH METHODS We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers. We checked reference lists of relevant articles. The most recent search was January 2023. SELECTION CRITERIA We included randomized controlled trials (RCTs) assessing the efficacy and safety of rTMS versus sham rTMS for PTSD in adults from any treatment setting, including veterans. Eligible trials employed at least five rTMS treatment sessions with both active and sham conditions. We included trials with combination interventions, where a pharmacological agent or psychotherapy was combined with rTMS for both intervention and control groups. We included studies meeting the above criteria regardless of whether they reported any of our outcomes of interest. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the risk of bias in accordance with Cochrane standards. Primary outcomes were PTSD severity immediately after treatment and serious adverse events during active treatment. Secondary outcomes were PTSD remission, PTSD response, PTSD severity at two follow-up time points after treatment, dropouts, and depression and anxiety severity immediately after treatment. MAIN RESULTS We included 13 RCTs in the review (12 published; 1 unpublished dissertation), with 577 participants. Eight studies included stand-alone rTMS treatment, four combined rTMS with an evidence-based psychotherapeutic treatment, and one investigated rTMS as an adjunctive to treatment-as-usual. Five studies were conducted in the USA, and some predominantly included white, male veterans. Active rTMS probably makes little to no difference to PTSD severity immediately following treatment (standardized mean difference (SMD) -0.14, 95% confidence interval (CI) -0.54 to 0.27; 3 studies, 99 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision (sample size insufficient to detect a difference of medium effect size). We deemed one study as having a low risk of bias and the remaining two as having 'some concerns' for risk of bias. A sensitivity analysis of change-from-baseline scores enabled inclusion of a greater number of studies (6 studies, 252 participants). This analysis yielded a similar outcome to our main analysis but also indicated significant heterogeneity in efficacy across studies, including two studies with a high risk of bias. Reported rates of serious adverse events were low, with seven reported (active rTMS: 6; sham rTMS: 1). The evidence is very uncertain about the effect of active rTMS on serious adverse events (odds ratio (OR) 5.26, 95% CI 0.26 to 107.81; 5 studies, 251 participants; very low-certainty evidence [Active rTMS: 23/1000, sham rTMS: 4/1000]). We downgraded the evidence by one level for risk of bias and two levels for imprecision. We rated four of five studies as having a high risk of bias, and the fifth as 'some concerns' for bias. We were unable to assess PTSD remission immediately after treatment as none of the included studies reported this outcome. AUTHORS' CONCLUSIONS Based on moderate-certainty evidence, our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation. However, significant heterogeneity in efficacy was detected when we included a larger number of studies in sensitivity analysis. We observed considerable variety in participant and protocol characteristics across studies included in this review. For example, studies tended to be weighted towards inclusion of either male veterans or female civilians. Studies varied greatly in terms of the proportion of the sample with comorbid depression. Study protocols differed in treatment design and stimulation parameters (e.g. session number/duration, treatment course length, stimulation intensity/frequency, location of stimulation). These differences may affect efficacy, particularly when considering interactions with participant factors. Reported rates of serious adverse events were very low (< 1%) across active and sham conditions. It is uncertain whether rTMS increases the risk of serious adverse event occurrence, as our certainty of evidence was very low. Studies frequently lacked clear definitions for serious adverse events, as well as detail on tracking/assessment of data and information on the safety population. Increased reporting on these elements would likely aid the advancement of both research and clinical recommendations of rTMS for PTSD. Currently, there is insufficient evidence to meta-analyze PTSD remission, PTSD treatment response, and PTSD severity at different periods post-treatment. Further research into these outcomes could inform the clinical use of rTMS. Additionally, the relatively large contribution of data from trials that focused on white male veterans may limit the generalizability of our conclusions. This could be addressed by prioritizing recruitment of more diverse participant samples.
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Affiliation(s)
- Randi Brown
- Clinical Psychology, Palo Alto University, Palo Alto, CA, USA
| | - Kirsten Cherian
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Katherine Jones
- Sheffield Centre for Health and Related Research, University of Sheffield, Sheffield, UK
| | - Robert Wickham
- Department of Psychological Sciences, Northern Arizona University, Flagstaff, AZ, USA
| | - Rowena Gomez
- Clinical Psychology, Palo Alto University, Palo Alto, CA, USA
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Gregory Sahlem
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
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Tillman GD, Morris EE, Bass C, Turner M, Watson K, Brooks JT, Rawlinson T, Kozel FA, Kraut MA, Motes MA, Hart J. P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment. Biol Psychol 2023; 182:108648. [PMID: 37482132 DOI: 10.1016/j.biopsycho.2023.108648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/25/2023]
Abstract
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.
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Affiliation(s)
- Gail D Tillman
- Callier Center, University of Texas at Dallas, Dallas, TX, USA.
| | | | - Christina Bass
- Callier Center, University of Texas at Dallas, Dallas, TX, USA
| | - Mary Turner
- Departments of Psychiatry University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Kelsey Watson
- Callier Center, University of Texas at Dallas, Dallas, TX, USA
| | - Jared T Brooks
- Callier Center, University of Texas at Dallas, Dallas, TX, USA
| | - Tyler Rawlinson
- Callier Center, University of Texas at Dallas, Dallas, TX, USA
| | - F Andrew Kozel
- Department of Behavioral Sciences and Social Medicine, Florida State University, Tallahassee, FL, USA
| | - Michael A Kraut
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Michael A Motes
- Callier Center, University of Texas at Dallas, Dallas, TX, USA
| | - John Hart
- Callier Center, University of Texas at Dallas, Dallas, TX, USA; Departments of Psychiatry University of Texas Southwestern Medical Center, Dallas, TX, USA; Departments of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Jiang C, Li Z, Wang J, Liu L, Luo G, Zheng X. Effectiveness of repetitive transcranial magnetic stimulation combined with a brief exposure procedure for post-stroke posttraumatic stress disorder. J Affect Disord 2023; 326:89-95. [PMID: 36717030 DOI: 10.1016/j.jad.2023.01.096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 01/21/2023] [Accepted: 01/25/2023] [Indexed: 01/30/2023]
Abstract
The incidence of posttraumatic stress disorder (PTSD) following stroke ranges from 6.5 % to 25 %. Presently few studies have focused on its treatment. Repetitive transcranial magnetic stimulation (rTMS) is often applied as a rehabilitation method after stroke, and it also represents a novel approach to PTSD. The aim of this study was to explore the effect of rTMS (or combined with a brief stroke re-exposure) on treating post-stroke PTSD. Sixty participants with post-stroke PTSD were randomly assigned into three groups (rTMS + brief exposure group, TMS + BE; rTMS alone group, TMS; sham treatment group, ST) and received 10 sessions of treatment accordingly over two weeks. Changes in PTSD symptoms (Impact of Event Scale-Revised, IES-R) were evaluated at pre-treatment (T1), the end of the first (T2), and the end of the second treatment week (T3). At the three-month follow-up (T4), a PTSD interview and IES-R assessment were given. Results showed that from T1 to T3, IES-R (and its intrusion subscale) scores of TMS + BE group and TMS group were significantly lower than the ST group, and the effect remained at three-month follow-up. The treatment effect was comparable between TMS + BE group and TMS group at T3, however, it was better for TMS + BE group than TMS group at T2, indicating a brief exposure promotes the effect of rTMS. At follow-up, the rates of PTSD were lower in TMS + BE group and TMS group than ST group. In conclusion, rTMS can effectively treat post-stroke PTSD and the effects may be accelerated by combining a brief exposure procedure. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100043444.
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Affiliation(s)
- Che Jiang
- Department of Neurosurgery, General Hospital of Southern Theater Command, 111 Liuhua Road, Guangzhou 510010, Guangdong, China.
| | - Zhensheng Li
- Department of Neurology, General Hospital of Southern Theatre Command, 111 Liuhua Road, Guangzhou 510010, Guangdong, China
| | - Jiajia Wang
- Department of Neurosurgery, General Hospital of Southern Theater Command, 111 Liuhua Road, Guangzhou 510010, Guangdong, China
| | - Leiyuan Liu
- Department of Neurosurgery, General Hospital of Southern Theater Command, 111 Liuhua Road, Guangzhou 510010, Guangdong, China
| | - Gaoquan Luo
- Department of Neurosurgery, General Hospital of Southern Theater Command, 111 Liuhua Road, Guangzhou 510010, Guangdong, China
| | - Xifu Zheng
- School of Psychology, South China Normal University, Guangzhou 510631, Guangdong, China.
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Marcolin KADS, da Cunha ÂBM, Yoneyama BC, Ribeiro TA. Effects of transcranial direct current stimulation (tDCS) in "Kiss nightclub fire" patients with post-traumatic stress disorder (PTSD): A phase II clinical trial. SAGE Open Med 2023; 11:20503121231160953. [PMID: 36993778 PMCID: PMC10041593 DOI: 10.1177/20503121231160953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 02/14/2023] [Indexed: 03/31/2023] Open
Abstract
Objective Considered the second biggest tragedy with fatal victims caused by fire, the Kiss nightclub fire tragedy that occurred in the interior of southern Brazil brought several problems to survivors. It is reported that 30-40% of victims of disasters can develop post-traumatic stress disorder. Application of repetitive transcranial magnetic stimulation has shown promising results in the treatment of post-traumatic stress disorder. Transcranial direct current stimulation similar to repetitive transcranial magnetic stimulation, a neuromodulation technique, has shown promise in treatment of neuropsychiatric disorders. Method A clinical trial was conducted from March 2015 to July 2016 in "KISS nightclub fire" disaster patients diagnosed with post-traumatic stress disorder without complete remission of symptoms, over 18 years, and who maintained pharmacological treatment. Treatment was given using electrodes as cathode (right dorsolateral prefrontal cortex) and anode (contralateral deltoid muscle); a current of 2 mA was used for 25 cm² area (0.08 mA/cm² current density); 30 min once a day for 10 days continuously. Patients assessed pre- and post-intervention, 30 days' and 90 days' post-intervention. Post-Traumatic Stress Disorder Checklist, Civilian version, Montreal Cognitive Assessment, and Hamilton Depression and Anxiety Rating Scale were used. Results One hundred forty-five subjects were screened and eight analyzed; 87.5% were female; 30.88 ± 7.74 years were of mean age. Post-intervention results: no cognitive impairment (Montreal Cognitive Assessment), 60% reduction in Hamilton Depression Rating Scale (moderate depression turns normal) (p < 0.001), 54.39% Hamilton Anxiety Rating Scale reduction (moderate-to-severe symptoms turn into mild symptoms) (p < 0.001), and 20% Post-Traumatic Stress Disorder Checklist, Civilian version scale decrease (high severity post-traumatic stress disorder symptoms turn moderate to moderately high severity) (p < 0.001). Post-traumatic stress disorder symptoms improvement was maintained 30-days post-intervention (Post-Traumatic Stress Disorder Checklist, Civilian version, p = 0.025) and improvement in symptoms of depression (Hamilton Depression Rating Scale, p = 0.006) and anxiety (Hamilton Anxiety Rating Scale, p = 0.028) in 90 days post-intervention. Conclusion Despite decrease over time, improvement in post-traumatic stress disorder, depression and anxiety symptoms was maintained throughout the first month after treatment. Transcranial direct current stimulation adjuvant can be an alternative treatment to refractory post-traumatic stress disorder, either as monotherapy or as treatment enhancement strategy. They can also be an option for patients who do not want or do not tolerate pharmacological management.
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Affiliation(s)
- Kathy Aleixo dos Santos Marcolin
- Postgraduate Program of Health Science, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil
- Psychiatrist, Psychiatry Service of University Hospital of Santa Maria (HUSM), Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil
| | - Ângelo Batista Miralha da Cunha
- Postgraduate Program of Health Science, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil
- Department of Psychiatry, Medicine School of Federal University of Santa Maria (UFSM), Rio Grande do Sul, Brazil
| | - Beatriz Capparros Yoneyama
- Psychiatrist, Psychiatry Service of University Hospital of Santa Maria (HUSM), Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil
| | - Tiango Aguiar Ribeiro
- Postgraduate Program of Health Science, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil
- Department of Surgery, Medicine School of Federal University of Santa Maria (UFSM), Rio Grande do Sul, Brazil
- Tiango Aguiar Ribeiro, Postgraduate Program of Health Science, Federal University of Santa Maria, Roraima Avenue, 1000 – in Federal Univeristy of Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil.
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The Use of Repetitive Transcranial Magnetic Stimulations for the Treatment of Post-Traumatic Stress Disorder: A Scoping Review. TRAUMA CARE 2022. [DOI: 10.3390/traumacare2020012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure in which brain neural activity is stimulated by the direct application of a magnetic field to the scalp. Despite its wide and continuous usage for the management of psychiatric disorders, the use of rTMS for post-traumatic stress disorder (PTSD) is not well established and evaluated by researchers. This scoping review seeks to explore the relevant literature available regarding the use of rTMS as a mode of treatment for PTSD, to map evidence in support of the use of rTMS for PTSD, and recommendations on future clinical and research work. Five databases were searched (MEDLINE, CINAHL, Psych INFO, SCOPUS, and EMBASE) to identify empirical studies and randomized controlled trials aimed at the treatment of PTSD with rTMS. A total of 10 studies were eligible for this review. The search results are up to date as of the date of the electronic data search of 20 December 2020. The frequencies applied in the studies ranged from low (1 Hz) to high (10 Hz) at different thresholds. Nine reported significant positive outcomes and PTSD symptoms improvement. rTMS was reported as well tolerated with no significant side effects. The application of rTMS for PTSD looks promising despite the diversity in terms of its outcomes and its clinical significance. Studies with well-defined stimulation parameters need to be conducted in the future.
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Petrosino NJ, Cosmo C, Berlow YA, Zandvakili A, van ’t Wout-Frank M, Philip NS. Transcranial magnetic stimulation for post-traumatic stress disorder. Ther Adv Psychopharmacol 2021; 11:20451253211049921. [PMID: 34733479 PMCID: PMC8558793 DOI: 10.1177/20451253211049921] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/09/2021] [Indexed: 01/14/2023] Open
Abstract
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. While current treatment options are effective for some, many individuals fail to respond to first-line psychotherapies and pharmacotherapy. Transcranial magnetic stimulation (TMS) has emerged over the past several decades as a noninvasive neuromodulatory intervention for psychiatric disorders including depression, with mounting evidence for its safety, tolerability, and efficacy in treating PTSD. While several meta-analyses of TMS for PTSD have been published to date showing large effect sizes on PTSD overall, there is marked variability between studies, making it difficult to draw simple conclusions about how best to treat patients. The following review summarizes over 20 years of the existing literature on TMS as a PTSD treatment, and includes nine randomized controlled trials and many other prospective studies of TMS monotherapy, as well as five randomized controlled trials investigating TMS combined with psychotherapy. While the majority of studies utilize repetitive TMS targeted to the right dorsolateral prefrontal cortex (DLPFC) at low frequency (1 Hz) or high frequency (10 or 20 Hz), others have used alternative frequencies, targeted other regions (most commonly the left DLPFC), or trialed different stimulation protocols utilizing newer TMS modalities such as synchronized TMS and theta-burst TMS (TBS). Although it is encouraging that positive outcomes have been shown, there is a paucity of studies directly comparing available approaches. Biomarkers, such as functional imaging and electroencephalography, were seldomly incorporated yet remain crucial for advancing our knowledge of how to predict and monitor treatment response and for understanding mechanism of action of TMS in this population. Effects on PTSD are often sustained for up to 2-3 months, but more long-term studies are needed in order to understand and predict duration of response. In short, while TMS appears safe and effective for PTSD, important steps are needed to operationalize optimal approaches for patients suffering from this disorder.
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Affiliation(s)
- Nicholas J. Petrosino
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Camila Cosmo
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Yosef A. Berlow
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Amin Zandvakili
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Mascha van ’t Wout-Frank
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S. Philip
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, 830 Chalkstone Avenue, Providence, RI 02908, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
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Cheng P, Zhou Y, Xu LZ, Chen YF, Hu RL, Zou YL, Li ZX, Zhang L, Shun Q, Yu X, Li LJ, Li WH. Clinical application of repetitive transcranial magnetic stimulation for post-traumatic stress disorder: A literature review. World J Clin Cases 2021; 9:8658-8665. [PMID: 34734044 PMCID: PMC8546820 DOI: 10.12998/wjcc.v9.i29.8658] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/30/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
The efficacy of traditional treatment for post-traumatic stress disorder (PTSD) is still unsatisfactory. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of various types of mental disorders, including PTSD. Although rTMS has been demonstrated to be effective in many cases, there are still arguments regarding its mechanism and protocol. This review aims to summarize the origin, development, principle, and future direction of rTMS and introduce this neuro-stimulation therapy to relevant clinicians.
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Affiliation(s)
- Peng Cheng
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ying Zhou
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Li-Zhi Xu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ya-Fei Chen
- Xiangya Medical School, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Ruo-Lin Hu
- Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Yi-Ling Zou
- Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ze-Xuan Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Li Zhang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Qi Shun
- Research Center for Brain Science and Human-like Intelligence, Xi’an Jiaotong University, Xi’an 710049, Shannxi Province, China
| | - Xun Yu
- Product Department, Solide Brain Medical Technology, Ltd., Xi’an 710043, Shannxi Province, China
| | - Ling-Jiang Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Wei-Hui Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
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10
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The Effects of Functionally Guided, Connectivity-Based rTMS on Amygdala Activation. Brain Sci 2021; 11:brainsci11040494. [PMID: 33924639 PMCID: PMC8070235 DOI: 10.3390/brainsci11040494] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/04/2021] [Accepted: 04/06/2021] [Indexed: 12/23/2022] Open
Abstract
While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected subcortical structures. Recent advances in task-related functional connectivity provide a means to better link superficial and deeper cortical sources with the possibility of increasing fronto-limbic modulation to induce stronger therapeutic effects. The objective of this pilot study was to test whether task-related, connectivity-based rTMS could modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). fMRI was collected to identify a node in the mPFC showing the strongest connectivity with the amygdala, as defined by psychophysiological interaction analysis. To promote Hebbian-like plasticity, and potentially stronger modulation, 5 Hz rTMS was applied while participants viewed frightening video-clips that engaged the fronto-limbic network. Significant increases in both the mPFC and amygdala were found for active rTMS compared to sham, offering promising preliminary evidence that functional connectivity-based targeting may provide a useful approach to treat network dysregulation. Further research is needed to better understand connectivity influences on rTMS effects to leverage this information to improve therapeutic applications.
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11
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Leong K, Chan P, Ong L, Zwicker A, Willan S, Lam RW, McGirr A. A Randomized Sham-controlled Trial of 1-Hz and 10-Hz Repetitive Transcranial Magnetic Stimulation (rTMS) of the Right Dorsolateral Prefrontal Cortex in Civilian Post-traumatic Stress Disorder: Un essai randomisé contrôlé simulé de stimulation magnétique transcrânienne repetitive (SMTr) de 1 Hz et 10 Hz du cortex préfrontal dorsolatéral droit dans le trouble de stress post-traumatique chez des civils. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2020; 65:770-778. [PMID: 32379487 PMCID: PMC7564694 DOI: 10.1177/0706743720923064] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Despite effective psychological and pharmacological treatments, there is a large unmet burden of illness in post-traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention and a putative treatment strategy for PTSD. The evidence base to date suggests that rTMS targeting the dorsolateral prefrontal cortex (DLPFC), in particular the right DLPFC, leads to improvements in PTSD symptoms. However, optimal stimulation parameters have yet to be determined. In this study, we examine the efficacy of high- and low-frequency rTMS of the right DLPFC using a randomized, double-blind, sham-controlled design in civilian PTSD. METHODS We conducted a 2-week single-site randomized sham-controlled trial of rTMS targeting the right DLPFC. We recruited civilians aged 19 to 70 with PTSD and randomized subjects with allocation concealment to daily 1-Hz rTMS, 10-Hz rTMS, or sham rTMS. The primary outcome was improvement in Clinician Administered PTSD Scale-IV (CAPS-IV). Secondary outcomes included change in depressive and anxiety symptoms. RESULTS We recruited 31 civilians with PTSD. One 1-Hz-treated patient developed transient suicidal ideation. Analyses revealed significant improvement in CAPS-IV symptoms in the 1-Hz group relative to sham (Hedges' g = -1.07) but not in the 10-Hz group. This was not attributable to changes in anxious or depressive symptomatology. Ten-Hz stimulation appeared to improve depressive symptoms compared to sham. CONCLUSION Low-frequency rTMS is efficacious in the treatment of civilian PTSD. Our data suggest that high-frequency rTMS of the right DLPFC is worthy of additional investigation for the treatment of depressive symptoms comorbid with PTSD.
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Affiliation(s)
- Kawai Leong
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Peter Chan
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada.,8166Brainstim Healthcare, Vancouver, British Columbia, Canada
| | - Larry Ong
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Amy Zwicker
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Sharon Willan
- 380154Vancouver General Hospital, British Columbia, Canada
| | - Raymond W Lam
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada
| | - Alexander McGirr
- Department of Psychiatry, 2129University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 2129University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada
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12
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Gouveia FV, Davidson B, Meng Y, Gidyk DC, Rabin JS, Ng E, Abrahao A, Lipsman N, Giacobbe P, Hamani C. Treating Post-traumatic Stress Disorder with Neuromodulation Therapies: Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, and Deep Brain Stimulation. Neurotherapeutics 2020; 17:1747-1756. [PMID: 32468235 PMCID: PMC7851279 DOI: 10.1007/s13311-020-00871-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Post-traumatic stress disorder (PTSD) is a prevalent and debilitating illness. While standard treatment with pharmacotherapy and psychotherapy may be effective, approximately 20 to 30% of patients remain symptomatic. These individuals experience depression, anxiety, and elevated rates of suicide. For treatment-resistant patients, there is a growing interest in the use of neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). We conducted a systematic review on the use of neuromodulation strategies for PTSD and pooled 13 randomized clinical trials (RCTs), 11 case series, and 6 case reports for analysis. Overall, most studies reported favorable outcomes in alleviating both PTSD and depressive symptoms. Although several RCTs described significant differences when active and sham stimulations were compared, others found marginal or nonsignificant differences between groups. Also positive were studies comparing PTSD symptoms before and after treatment. The side effect profile with all 3 modalities was found to be low, with mostly mild adverse events being reported. Despite these encouraging data, several aspects remain unknown. Given that PTSD is a highly heterogeneous condition that can be accompanied by distinct psychiatric diagnoses, defining a unique treatment for this patient population can be quite challenging. There has also been considerable variation across trials regarding stimulation parameters, symptomatic response, and the role of adjunctive psychotherapy. Future studies are needed to address these issues.
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Affiliation(s)
| | - Benjamin Davidson
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Ying Meng
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | | | - Jennifer S Rabin
- Sunnybrook Research Institute, 2075 Bayview Av, S126, Toronto, ON, M4N3M5, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Enoch Ng
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Agessandro Abrahao
- Sunnybrook Research Institute, 2075 Bayview Av, S126, Toronto, ON, M4N3M5, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Nir Lipsman
- Sunnybrook Research Institute, 2075 Bayview Av, S126, Toronto, ON, M4N3M5, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Peter Giacobbe
- Sunnybrook Research Institute, 2075 Bayview Av, S126, Toronto, ON, M4N3M5, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada
| | - Clement Hamani
- Sunnybrook Research Institute, 2075 Bayview Av, S126, Toronto, ON, M4N3M5, Canada.
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada.
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13
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Bremner JD, Gurel NZ, Wittbrodt MT, Shandhi MH, Rapaport MH, Nye JA, Pearce BD, Vaccarino V, Shah AJ, Park J, Bikson M, Inan OT. Application of Noninvasive Vagal Nerve Stimulation to Stress-Related Psychiatric Disorders. J Pers Med 2020; 10:E119. [PMID: 32916852 PMCID: PMC7563188 DOI: 10.3390/jpm10030119] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. METHODS New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. RESULTS This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. CONCLUSIONS nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
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Affiliation(s)
- James Douglas Bremner
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; (M.T.W.); (M.H.R.)
- Department of Radiology, Emory University School of Medicine, Atlanta, GA 30322, USA;
- Atlanta VA Medical Center, Decatur, GA 30033, USA; (A.J.S.); (J.P.)
| | - Nil Z. Gurel
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; (N.Z.G.); (M.H.S.); (O.T.I.)
| | - Matthew T. Wittbrodt
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; (M.T.W.); (M.H.R.)
| | - Mobashir H. Shandhi
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; (N.Z.G.); (M.H.S.); (O.T.I.)
| | - Mark H. Rapaport
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; (M.T.W.); (M.H.R.)
| | - Jonathon A. Nye
- Department of Radiology, Emory University School of Medicine, Atlanta, GA 30322, USA;
| | - Bradley D. Pearce
- Department of Epidemiology, Rollins School of Public Health, Atlanta, GA 30322, USA; (B.D.P.); (V.V.)
| | - Viola Vaccarino
- Department of Epidemiology, Rollins School of Public Health, Atlanta, GA 30322, USA; (B.D.P.); (V.V.)
- Department of Medicine, Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Amit J. Shah
- Atlanta VA Medical Center, Decatur, GA 30033, USA; (A.J.S.); (J.P.)
- Department of Epidemiology, Rollins School of Public Health, Atlanta, GA 30322, USA; (B.D.P.); (V.V.)
- Department of Medicine, Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Jeanie Park
- Atlanta VA Medical Center, Decatur, GA 30033, USA; (A.J.S.); (J.P.)
- Department of Medicine, Renal Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Marom Bikson
- Department of Biomedical Engineering, City University of New York, New York, NY 10010, USA;
| | - Omer T. Inan
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; (N.Z.G.); (M.H.S.); (O.T.I.)
- Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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14
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Koek RJ, Roach J, Athanasiou N, van 't Wout-Frank M, Philip NS. Neuromodulatory treatments for post-traumatic stress disorder (PTSD). Prog Neuropsychopharmacol Biol Psychiatry 2019; 92:148-160. [PMID: 30641094 DOI: 10.1016/j.pnpbp.2019.01.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 12/19/2018] [Accepted: 01/10/2019] [Indexed: 12/12/2022]
Abstract
Electroconvulsive therapy has been used successfully in some individuals with posttraumatic stress disorder (PTSD) whose symptoms have not improved with other treatments. But there are only a few reports. Meanwhile, an array of new neuromodulation strategies, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, trigeminal nerve stimulation, and deep brain stimulation have been developed and applied experimentally in the treatment of other psychiatric disorders. This article will review the clinical evidence and mechanistic basis for their use in PTSD.
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Affiliation(s)
- Ralph J Koek
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; Sepulveda Ambulatory Care Center, Veterans Administration Greater Los Angeles Healthcare System, North Hills, CA, USA.
| | - Janine Roach
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; Oliveview Medical Center, Sylmar, CA, USA
| | - Nicholas Athanasiou
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; San Fernando Mental Health Center, Granada Hills, CA, USA
| | - Mascha van 't Wout-Frank
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S Philip
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA; VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, USA
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15
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Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. J ECT 2019; 35:53-60. [PMID: 29952863 DOI: 10.1097/yct.0000000000000505] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES This is a small preliminary but novel study assessing the feasibility of repetitive transcranial magnetic stimulation (rTMS) delivery to veterans with posttraumatic stress disorder (PTSD) while they simultaneously receive prolonged exposure (PE) therapy. METHODS A prospective, randomized, double-blinded, active sham-controlled design combined weekly sessions of rTMS and standard PE at the Veterans Administration Hospital. Eight adult patients received a full course of protocol-driven PE therapy and were randomly assigned to receive either rTMS or sham rTMS. Repetitive transcranial magnetic stimulation was delivered to the right or left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hz, 5-second train duration, and 10-second intertrain interval for 30 minutes (6000 pulses) weekly for 5 weeks (30,000 stimuli). RESULTS Of the 12 veterans consented, 8 completed the study treatment protocol. The dropout rate was 34%, roughly equivalent to the pooled average dropout rates observed in traditional PE therapy with Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, suggesting that veterans had no difficulty tolerating the addition of rTMS to PE therapy and that this is a feasible study design for larger trials in the future. Clinician-Administered PTSD Symptom scores reflected a general nonsignificant trend toward improvement, and subjects with comorbid major depression appeared to experience significant antidepressant benefit with treatment despite the fact that the doses used in this protocol were much smaller than those used to treat patients with major depressive disorder. CONCLUSIONS This pilot study demonstrates the safety and feasibility of rTMS delivery to PTSD patients while they simultaneously receive PE. This unique approach to the treatment of PTSD highlights the need for further studies with larger sample sizes to assess treatment outcomes.
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16
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Lebois LAM, Seligowski AV, Wolff JD, Hill SB, Ressler KJ. Augmentation of Extinction and Inhibitory Learning in Anxiety and Trauma-Related Disorders. Annu Rev Clin Psychol 2019; 15:257-284. [PMID: 30698994 DOI: 10.1146/annurev-clinpsy-050718-095634] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Although the fear response is an adaptive response to threatening situations, a number of psychiatric disorders feature prominent fear-related symptoms caused, in part, by failures of extinction and inhibitory learning. The translational nature of fear conditioning paradigms has enabled us to develop a nuanced understanding of extinction and inhibitory learning based on the molecular substrates to systems neural circuitry and psychological mechanisms. This knowledge has facilitated the development of novel interventions that may augment extinction and inhibitory learning. These interventions include nonpharmacological techniques, such as behavioral methods to implement during psychotherapy, as well as device-based stimulation techniques that enhance or reduce activity in different regions of the brain. There is also emerging support for a number of psychopharmacological interventions that may augment extinction and inhibitory learning specifically if administered in conjunction with exposure-based psychotherapy. This growing body of research may offer promising novel techniques to address debilitating transdiagnostic fear-related symptoms.
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Affiliation(s)
- Lauren A M Lebois
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Antonia V Seligowski
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Jonathan D Wolff
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Sarah B Hill
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Kerry J Ressler
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
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17
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Kozel FA. Clinical Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder, Generalized Anxiety Disorder, and Bipolar Disorder. Psychiatr Clin North Am 2018; 41:433-446. [PMID: 30098656 DOI: 10.1016/j.psc.2018.04.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is being investigated for psychiatric disorders such as posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and both phases of bipolar disorder. Case series, open trials, and randomized controlled studies have demonstrated preliminary support for treating PTSD with rTMS alone as well as with rTMS combined with psychotherapy. Similarly, there is some evidence that GAD can be treated with rTMS. The results for treating either phase of bipolar disorder are mixed with most of the current studies showing lack of benefit over sham. Further study is required before rTMS can be recommended for these disorders.
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Affiliation(s)
- F Andrew Kozel
- Mental Health and Behavioral Sciences & HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Administration Hospital and Clinics, 116A, 13000 Bruce B. Downs Boulevard, Tampa, FL 33612, USA; Department of Psychiatry and Behavioral Neurosciences, University of South Florida, 3515 E Fletcher Avenue, Tampa, FL 33613, USA.
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18
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Ahmadizadeh MJ, Rezaei M. Unilateral right and bilateral dorsolateral prefrontal cortex transcranial magnetic stimulation in treatment post-traumatic stress disorder: A randomized controlled study. Brain Res Bull 2018; 140:334-340. [DOI: 10.1016/j.brainresbull.2018.06.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 05/30/2018] [Accepted: 06/01/2018] [Indexed: 01/07/2023]
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19
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Kozel FA, Motes MA, Didehbani N, DeLaRosa B, Bass C, Schraufnagel CD, Jones P, Morgan CR, Spence JS, Kraut MA, Hart J. Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. J Affect Disord 2018; 229:506-514. [PMID: 29351885 DOI: 10.1016/j.jad.2017.12.046] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 11/22/2017] [Accepted: 12/26/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND The objective was to test whether repetitive Transcranial Magnetic Stimulation (rTMS) just prior to Cognitive Processing Therapy (CPT) would significantly improve the clinical outcome compared to sham rTMS prior to CPT in veterans with PTSD. METHODS Veterans 18-60 years of age with current combat-related PTSD symptoms were randomized, using a 1:1 ratio in a parallel design, to active (rTMS+CPT) versus sham (sham+CPT) rTMS just prior to weekly CPT for 12-15 sessions. Blinded raters evaluated veterans at baseline, after the 5th and 9th treatments, and at 1, 3, and 6 months post-treatment. Clinician Administered PTSD Scale (CAPS) was the primary outcome measure with the PTSD Checklist (PCL) as a secondary outcome measure. The TMS coil (active or sham) was positioned over the right dorsolateral prefrontal cortex (110% MT, 1Hz continuously for 30min, 1800 pulses/treatment). RESULTS Of the 515 individuals screened for the study, 103 participants were randomized to either active (n = 54) or sham rTMS (n = 49). Sixty-two participants (60%) completed treatment and 59 (57%) completed the 6-month assessment. The rTMS+CPT group showed greater symptom reductions from baseline on both CAPS and PCL across CPT sessions and follow-up assessments, t(df ≥ 325) ≤ -2.01, p ≤ 0.023, one-tailed and t(df ≥ 303) ≤ -2.14, p ≤ 0.017, one-tailed, respectively. LIMITATIONS Participants were predominantly male and limited to one era of conflicts as well as those who could safely undergo rTMS. CONCLUSIONS The addition of rTMS to CPT compared to sham with CPT produced significantly greater PTSD symptom reduction early in treatment and was sustained up to six months post-treatment.
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Affiliation(s)
- F Andrew Kozel
- Mental Health and Behavioral Sciences & HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA.
| | | | | | | | | | | | | | | | | | - Michael A Kraut
- Department of Radiology and Radiologic Sciences, Johns Hopkins, University School of Medicine, Baltimore, MD, USA
| | - John Hart
- University of Texas, Dallas, Dallas, TX, USA; Depts. of Neurology and Neurotherapeutics and Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
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20
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Kosman KA, Lonergan BB, Awasthi S, Hinchman CA, Stern AP. Emerging areas of transcranial magnetic stimulation use in psychiatry. FUTURE NEUROLOGY 2017. [DOI: 10.2217/fnl-2017-0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Transcranial magnetic stimulation (TMS) is most widely known clinically as a treatment for medication-refractory major depressive disorder, but it holds promise in a number of other areas. In addition to emerging neurologic areas of investigation such as in mild cognitive impairment, dementia, Parkinson's disease and stroke rehab, novel approaches to psychiatric conditions are also being explored. This review provides a critical condensation of the available data assessing the efficacy of TMS in the treatment of other psychiatric conditions, namely bipolar disorder, substance use, post-traumatic stress disorder and other anxiety disorders. Each section details the field's current accumulation of evidence of the respective condition's pathophysiology in the context of a discussion of the relevant therapeutic target(s) of TMS. Each section then reviews both positive and negative studies evaluating TMS in clinical practice. Given the relative tolerability and proven efficacy of TMS in treatment-resistant depression (TRD), further study to determine its therapeutic effect in other psychiatric entities is warranted.
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Affiliation(s)
- Katherine A Kosman
- Harvard Longwood Psychiatry Residency Training Program, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Rabb-2, Boston, MA 02215, USA
| | - Brady B Lonergan
- Harvard Longwood Psychiatry Residency Training Program, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Rabb-2, Boston, MA 02215, USA
| | - Samir Awasthi
- Harvard Longwood Psychiatry Residency Training Program, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Rabb-2, Boston, MA 02215, USA
| | - Carrie A Hinchman
- Berenson Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, MA, USA
| | - Adam P Stern
- Berenson Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, MA, USA
- Department of Psychiatry, Beth Israel Deaconess Medical Center, MA, USA
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21
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Yan T, Xie Q, Zheng Z, Zou K, Wang L. Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis. J Psychiatr Res 2017; 89:125-135. [PMID: 28278422 DOI: 10.1016/j.jpsychires.2017.02.021] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 01/18/2017] [Accepted: 02/09/2017] [Indexed: 01/11/2023]
Abstract
Posttraumatic stress disorder (PTSD) is a psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective for treating PTSD, but whether different frequencies have different effects remains controversial. We conducted this systematic review and meta-analysis to address this question. We searched the literature for studies written in English or Chinese in 9 electronic databases from the databases' inception to August 1, 2016. Additional articles were identified from the reference lists of identified studies and from personal reference collections. Eighteen articles were included, and 11 were suitable for the meta-analysis (Combined sample size was 377 (217 in active rTMS groups, 160 in sham-controlled groups)). Low-frequency (LF) rTMS resulted in a significant reduction in the PTSD total score and the depression score (1. PTSD total score: pooled SMD, 0.92; CI, 0.11-1.72; 2. Depression: pooled SMD, 0.54; CI, 0.08-1.00). High-frequency (HF) rTMS showed the following results: 1. PTSD total score: pooled SMD, 3.24; CI, 2.24-4.25; 2. re-experiencing: pooled SMD, -1.77; CI, -2.49-(-1.04); 3. Avoidance: pooled SMD, -1.57; CI, -2.50-(-0.84); 4. hyperarousal: pooled SMD, -1.32; CI, -2.17-(-0.47); 5. depression: pooled SMD, 1.92; CI, 0.80-3.03; and 6. Anxiety: pooled SMD, 2.67; CI, 1.82-3.52. Therefore, both HF and LF rTMS can alleviate PTSD symptoms. Although the evidence is extremely limited, LF rTMS can reduce overall PTSD and depression symptoms. HF rTMS can improve the main and related symptoms of PTSD. However, additional research is needed to substantiate these findings.
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Affiliation(s)
- Tingting Yan
- Department of Disaster Medical Science, Sichuan University, Institute for Disaster Management and Reconstruction, Sichuan University, Chengdu, 610041, PR China.
| | - Qinglian Xie
- Department of Psychiatry, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Zhong Zheng
- Department of Neurobiological Examine Centre, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Ke Zou
- Department of Neurobiological Examine Centre, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Lijuan Wang
- Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial Peoples Hospital, Chengdu, 610041, PR China
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Treatment-refractory posttraumatic stress disorder (TRPTSD): a review and framework for the future. Prog Neuropsychopharmacol Biol Psychiatry 2016; 70:170-218. [PMID: 26854815 DOI: 10.1016/j.pnpbp.2016.01.015] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 01/29/2016] [Accepted: 01/29/2016] [Indexed: 01/04/2023]
Abstract
Post-traumatic stress disorder (PTSD) is a serious psychiatric consequence of trauma that occurs in a proportion of individuals exposed to life-threatening events. Trauma-focused psychotherapy is often recommended as first choice for those who do not recover spontaneously. But many individuals require medications. In the US, only paroxetine (PRX) and sertraline (SRT) are FDA approved for PTSD. But response and remission rates with these medications are low, so numerous other pharmacologic interventions have been tried. To date, there has not been a systematic review of the data on what are the best next-step pharmacologic strategies for individuals who fail standard treatments. To that end, we review 168 published trials of medications other than PRX or SRT and provide a detailed analysis of the 88/168 studies that describe alternative pharmacologic interventions in patients refractory to other treatment. We also review clinical factors relevant to treatment-refractory PTSD; the neurobiology of extinction, as well as evidence-based psychotherapy and neuromodulation strategies for this condition.
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Iannone A, Cruz APDM, Brasil-Neto JP, Boechat-Barros R. Transcranial magnetic stimulation and transcranial direct current stimulation appear to be safe neuromodulatory techniques useful in the treatment of anxiety disorders and other neuropsychiatric disorders. ARQUIVOS DE NEURO-PSIQUIATRIA 2016; 74:829-835. [DOI: 10.1590/0004-282x20160115] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 06/21/2016] [Indexed: 12/28/2022]
Abstract
ABSTRACT Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS. The use of off-label therapeutic TMS or tDCS tends to occur in the setting of diseases that are notoriously resistant to other treatment modalities. Here we discuss the case of anxiety disorders, namely panic and post-traumatic stress disorders, highlighting the uncertainties and potential problems and benefits of the clinical use of these neuromodulatory techniques at the current stage of knowledge.
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Philip NS, Ridout SJ, Albright SE, Sanchez G, Carpenter LL. 5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. J Trauma Stress 2016; 29:93-6. [PMID: 26748883 PMCID: PMC4849266 DOI: 10.1002/jts.22065] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.
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Affiliation(s)
- Noah S. Philip
- Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island, USA
| | - Samuel J. Ridout
- Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Sarah E. Albright
- Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island, USA
| | - George Sanchez
- Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island, USA
| | - Linda L. Carpenter
- Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA
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Clark C, Cole J, Winter C, Williams K, Grammer G. A Review of Transcranial Magnetic Stimulation as a Treatment for Post-Traumatic Stress Disorder. Curr Psychiatry Rep 2015; 17:83. [PMID: 26324821 DOI: 10.1007/s11920-015-0621-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
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.
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Affiliation(s)
- Caroline Clark
- Department of Psychiatry, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD, 20889, USA
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George MS, Baron Short E, Kerns SE, Li X, Hanlon C, Pelic C, Taylor JJ, Badran BW, Borckardt JJ, Williams N, Fox J. Therapeutic Applications of rTMS for Psychiatric and Neurological Conditions. Brain Stimul 2015. [DOI: 10.1002/9781118568323.ch12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
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Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing. Neuroimage 2014; 101:193-203. [DOI: 10.1016/j.neuroimage.2014.07.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Revised: 07/04/2014] [Accepted: 07/05/2014] [Indexed: 11/18/2022] Open
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Herrold AA, Kletzel SL, Harton BC, Chambers RA, Jordan N, Pape TLB. Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders. Neural Regen Res 2014; 9:1712-30. [PMID: 25422632 PMCID: PMC4238159 DOI: 10.4103/1673-5374.143408] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2014] [Indexed: 12/13/2022] Open
Abstract
Alcohol use disorder (AUD), mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD) commonly co-occur (AUD + mTBI + PTSD). These conditions have overlapping symptoms which are, in part, reflective of overlapping neuropathology. These conditions become problematic because their co-occurrence can exacerbate symptoms. Therefore, treatments must be developed that are inclusive to all three conditions. Repetitive transcranial magnetic stimulation (rTMS) is non-invasive and may be an ideal treatment for co-occurring AUD + mTBI + PTSD. There is accumulating evidence on rTMS as a treatment for people with AUD, mTBI, and PTSD each alone. However, there are no published studies to date on rTMS as a treatment for co-occurring AUD + mTBI + PTSD. This review article advances the knowledge base for rTMS as a treatment for AUD + mTBI + PTSD. This review provides background information about these co-occurring conditions as well as rTMS. The existing literature on rTMS as a treatment for people with AUD, TBI, and PTSD each alone is reviewed. Finally, neurobiological findings in support of a theoretical model are discussed to inform TMS as a treatment for co-occurring AUD + mTBI + PTSD. The peer-reviewed literature was identified by targeted literature searches using PubMed and supplemented by cross-referencing the bibliographies of relevant review articles. The existing evidence on rTMS as a treatment for these conditions in isolation, coupled with the overlapping neuropathology and symptomology of these conditions, suggests that rTMS may be well suited for the treatment of these conditions together.
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Affiliation(s)
- Amy A. Herrold
- Edward Hines Jr. VA Hospital, Research Service PO Box 5000 (M/C 151H), Hines, IL, USA
- The Department of Veterans Affairs (VA), Center for Innovation for Complex Chronic Healthcare, Edward Hines Jr. VA Hospital, PO Box 5000 (M/C 151H), Hines, IL, USA
- Department of Psychiatry & Behavioral Sciences, Northwestern University Feinberg School of Medicine, 446 East Ontario, #7-200, Chicago, IL, USA
| | - Sandra L. Kletzel
- The Department of Veterans Affairs (VA), Center for Innovation for Complex Chronic Healthcare, Edward Hines Jr. VA Hospital, PO Box 5000 (M/C 151H), Hines, IL, USA
| | - Brett C. Harton
- Chicago Association for Research and Education in Science, Hines, IL, USA
| | - R. Andrew Chambers
- Department of Psychiatry, Laboratory for Translational Neuroscience of Dual Diagnosis & Development, Neuroscience Research Center, Indiana University School of Medicine, 320 West 15 Street, Indianapolis, IN, USA
| | - Neil Jordan
- The Department of Veterans Affairs (VA), Center for Innovation for Complex Chronic Healthcare, Edward Hines Jr. VA Hospital, PO Box 5000 (M/C 151H), Hines, IL, USA
- Department of Psychiatry & Behavioral Sciences, Northwestern University Feinberg School of Medicine, 446 East Ontario, #7-200, Chicago, IL, USA
| | - Theresa Louise-Bender Pape
- Edward Hines Jr. VA Hospital, Research Service PO Box 5000 (M/C 151H), Hines, IL, USA
- The Department of Veterans Affairs (VA), Center for Innovation for Complex Chronic Healthcare, Edward Hines Jr. VA Hospital, PO Box 5000 (M/C 151H), Hines, IL, USA
- Northwestern University Feinberg School of Medicine, Department of Physical Medicine and Rehabilitation, Office of Medical Educ. (1574), 345 E. Superior St., Chicago, IL, USA
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29
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Berlim MT, Van Den Eynde F. Repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex for treating posttraumatic stress disorder: an exploratory meta-analysis of randomized, double-blind and sham-controlled trials. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2014; 59:487-96. [PMID: 25565694 PMCID: PMC4168811 DOI: 10.1177/070674371405900905] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 02/01/2014] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) has yielded promising results as a treatment for posttraumatic stress disorder (PTSD). However, to date, no quantitative review of its clinical utility has been published. METHOD We searched for randomized and sham-controlled trials from 1995 to March 2013 using MEDLINE, Embase, PsycINFO, CENTRAL, and SCOPUS. We then performed an exploratory random effects meta-analysis. RESULTS Studies on rTMS applied to the right DLPFC included 64 adults with PTSD. The pooled Hedges g effect size for pre and post changes in clinician-rated and self-reported PTSD symptoms were, respectively, 1.65 (P < 0.001) and 1.91 (P < 0.001), indicating significant and large-sized differences in outcome favouring active rTMS. Also, there were significant pre and post decreases with active rTMS in overall anxiety (Hedges g = 1.24; P = 0.02) and depressive (Hedges g = 0.85; P < 0.001) symptoms. Dropout rates at study end did not differ between active and sham rTMS groups. Regarding rTMS applied to the left DLPFC, there is only one study published to date (using a high frequency protocol), and its results showed that active rTMS seems to be superior overall to sham rTMS. CONCLUSIONS Our exploratory meta-analysis shows that active rTMS applied to the DLPFC seems to be effective and acceptable for treating PTSD. However, the small number of subjects included in the analyses limits the generalizability of these findings. Future studies should include larger samples and deliver optimized stimulation parameters.
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Affiliation(s)
- Marcelo T Berlim
- Assistant Professor, Department of Psychiatry, McGill University, Montreal, Quebec; Director, Neuromodulation Research Clinic, Douglas Mental Health University Institute, Montreal, Quebec
| | - Frederique Van Den Eynde
- Assistant Professor, Department of Psychiatry, McGill University, Montreal, Quebec; Co-Director, Neuromodulation Research Clinic, Douglas Mental Health University Institute, Montreal, Quebec
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30
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Karsen EF, Watts BV, Holtzheimer PE. Review of the Effectiveness of Transcranial Magnetic Stimulation for Post-traumatic Stress Disorder. Brain Stimul 2014; 7:151-7. [DOI: 10.1016/j.brs.2013.10.006] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Revised: 10/18/2013] [Accepted: 10/23/2013] [Indexed: 01/11/2023] Open
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31
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Pigot M, Loo C, Sachdev P. Repetitive transcranial magnetic stimulation as treatment for anxiety disorders. Expert Rev Neurother 2014; 8:1449-55. [DOI: 10.1586/14737175.8.10.1449] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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32
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Sánchez-Escandón O, Arana-Lechuga Y, Terán-Pérez G, Ruiz-Chow Á, Esqueda-Leon E, González-Robles RO, Shkurovich-Bialik P, Collado-Corona MÁ, Velázquez-Moctezuma J. Transcraneal Magnetic Stimulation Improves Sleep Parameters in Patients Affected with Imsomnia Associated to Electroencephalographic Abnormalities. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/nm.2014.51010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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33
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Transcranial Magnetic Stimulation (TMS) Clinical Applications: Therapeutics. TRANSCRANIAL MAGNETIC STIMULATION 2014. [DOI: 10.1007/978-1-4939-0879-0_12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Nam DH, Pae CU, Chae JH. Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled Study. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2013; 11:96-102. [PMID: 24023554 PMCID: PMC3766761 DOI: 10.9758/cpn.2013.11.2.96] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Revised: 06/25/2013] [Accepted: 07/20/2013] [Indexed: 12/16/2022]
Abstract
Objective Several studies have suggested that repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex may be useful in the treatment of posttraumatic stress disorder (PTSD). The aim of this study was to compare the effect of rTMS on the right prefrontal cortex with that of sham stimulation among patients with PTSD. Methods In total, 18 patients with PTSD were randomly assigned to the 1-Hz low-frequency rTMS group or the sham group for 3 weeks. Primary efficacy measures were the Clinician-Administered PTSD Scale (CAPS) and its subscales, assessed at baseline and at 2, 4, and 8 weeks. Results All CAPS scores improved significantly over the study period. We found significant differences in the re-experiencing scores (F=7.47, p=0.004) and total scores (F=6.45, p=0.008) on the CAPS. The CAPS avoidance scores showed a trend toward significance (F=2.74, p=0.055), but no significant differences in the CAPS hyperarousal scores were observed. Conclusion The present study showed low-frequency rTMS to be an effective and tolerable option for the treatment of PTSD. Trials using variable indices of rTMS to the right prefrontal cortex and explorations of the differences in the effects on specific symptom clusters may be promising avenues of research regarding the use of rTMS for PTSD.
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Affiliation(s)
- Dong-Hyun Nam
- Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Korea
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Bogdanova Y, Verfaellie M. Cognitive sequelae of blast-induced traumatic brain injury: recovery and rehabilitation. Neuropsychol Rev 2012; 22:4-20. [PMID: 22350691 PMCID: PMC4372457 DOI: 10.1007/s11065-012-9192-3] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Accepted: 02/01/2012] [Indexed: 01/01/2023]
Abstract
Blast-related traumatic brain injury (bTBI) poses a significant concern for military personnel engaged in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). Given the highly stressful context in which such injury occurs, psychiatric comorbidities are common. This paper provides an overview of mild bTBI and discusses the cognitive sequelae and course of recovery typical of mild TBI (mTBI). Complicating factors that arise in the context of co-morbid posttraumatic stress disorder (PTSD) are considered with regard to diagnosis and treatment. Relatively few studies have evaluated the efficacy of cognitive rehabilitation in civilian mTBI, but we discuss cognitive training approaches that hold promise for addressing mild impairments in executive function and memory, akin to those seen in OEF/OIF veterans with bTBI and PTSD. Further research is needed to address the patient and environmental characteristics associated with optimal treatment outcome.
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Affiliation(s)
- Yelena Bogdanova
- VA Boston Healthcare System, Memory Disorders Research Center, Boston University School of Medicine, Boston, MA 02130, USA.
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36
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A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder. Brain Stimul 2012; 5:38-43. [DOI: 10.1016/j.brs.2011.02.002] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2010] [Revised: 01/21/2011] [Accepted: 02/04/2011] [Indexed: 02/08/2023] Open
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Novakovic V, Sher L, Lapidus KA, Mindes J, A.Golier J, Yehuda R. Brain stimulation in posttraumatic stress disorder. Eur J Psychotraumatol 2011; 2:EJPT-2-5609. [PMID: 22893803 PMCID: PMC3402102 DOI: 10.3402/ejpt.v2i0.5609] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2010] [Revised: 07/25/2011] [Accepted: 09/19/2011] [Indexed: 01/21/2023] Open
Abstract
Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration.
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Affiliation(s)
- Vladan Novakovic
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
| | - Leo Sher
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
| | - Kyle A.B. Lapidus
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
| | - Janet Mindes
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
| | - Julia A.Golier
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
| | - Rachel Yehuda
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
- Department of Psychiatry, James J. Peters VA Medical Center, New York, NY, USA
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Baek K, Chae JH, Jeong J. The effect of repetitive transcranial magnetic stimulation on fear extinction in rats. Neuroscience 2011; 200:159-65. [PMID: 21989475 DOI: 10.1016/j.neuroscience.2011.09.050] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2010] [Revised: 09/26/2011] [Accepted: 09/26/2011] [Indexed: 11/18/2022]
Abstract
Facilitating fear extinction is clinically important to improve the efficacy of current exposure therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD). The aim of this study was to determine if repeated transcranial magnetic stimulation (rTMS) facilitates fear extinction in rats, especially when paired with exposure to a conditioned stimulus (CS). Thirty-five rats were conditioned to a tone CS by pairing the tone with an electric foot shock as an aversive unconditioned stimulus (US). We assessed the effects of 10 Hz rTMS before fear extinction (experiment 1) and rTMS paired with CS during extinction (experiment 2) on the following day. Fear responses of the rats were estimated using the level of freezing upon tone stimulus and were compared between the rTMS and corresponding sham groups. The rats treated with rTMS before fear extinction showed no difference in freezing time when compared with the sham group. However, the rats treated with rTMS paired with CS during extinction showed significantly less freezing behavior than the sham group, and this enhancement of fear extinction remained after 24 h without further stimulation. This finding suggests that high-frequency rTMS paired with trauma-reminding stimuli enhances fear extinction and that rTMS in conjunction with exposure therapy is potentially useful for facilitating extinction memory in the treatment of PTSD.
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Affiliation(s)
- K Baek
- Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
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39
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Wassermann EM, Zimmermann T. Transcranial magnetic brain stimulation: therapeutic promises and scientific gaps. Pharmacol Ther 2011; 133:98-107. [PMID: 21924290 DOI: 10.1016/j.pharmthera.2011.09.003] [Citation(s) in RCA: 145] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Accepted: 08/12/2011] [Indexed: 01/19/2023]
Abstract
Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists studying the human motor system, TMS now has a growing list of applications in clinical and basic neuroscience. Although we understand many of its effects at the system level, detailed knowledge of its actions, particularly as a modulator of neural activity, has lagged, due mainly to the lack of suitable non-human models. Nevertheless, these gaps have not blocked the therapeutic application of TMS in brain disorders. Moderate success has been achieved in treating disorders such as depression, where the U.S. Food and Drug Administration has cleared a TMS system for therapeutic use. In addition, there are small, but promising, bodies of data on the treatment of schizophrenic auditory hallucinations, tinnitus, anxiety disorders, neurodegenerative diseases, hemiparesis, and pain syndromes. Some other nascent areas of study also exist. While the fate of TMS as a therapeutic modality depends on continued innovation and experimentation, economic and other factors may be decisive.
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Affiliation(s)
- Eric M Wassermann
- Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
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RETRACTED ARTICLE: Transcranial Magnetic Stimulation: Recent Advancement and Neuroethical Issues. NEUROETHICS-NETH 2011. [DOI: 10.1007/s12152-011-9099-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Patients with posttraumatic stress disorder show decreased cognitive control: evidence from dichotic listening. J Int Neuropsychol Soc 2011; 17:344-53. [PMID: 21338561 DOI: 10.1017/s1355617710001736] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The influence of posttraumatic stress disorder (PTSD) on cognitive control and auditory attention modulation was examined with the use of a dichotic-listening (DL) task. The participants were 45 war-exposed refugees. The PTSD group comprised 22 participants meeting the DSM-IV criteria for PTSD, and the Control group comprised 23 war-exposed participants without PTSD. Both groups were tested with a consonant-vowel syllables DL task under three different attentional instructions. The two groups did not differ in the non-forced and forced-right conditions and showed, as expected, right-ear advantages. The Control group showed, as expected, a left-ear advantage in the forced-left (FL) condition. However, the PTSD group continued to show a right-ear advantage--and only minor modulation of the performance during the FL condition. This finding suggests that PTSD is associated with a reduced capacity for top-down attentional control of a bottom-up or stimulus-driven effect. The result shows that participants with PTSD have impaired cognitive control functions when tested on information processing of neutral stimuli.
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Asbjørnsen AE. Dichotic listening performance suggests right hemisphere involvement in PTSD. Laterality 2010; 16:401-22. [PMID: 21161816 DOI: 10.1080/13576501003702655] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The present study focuses on language laterality as measured with dichotic listening (DL) to consonant-vowel syllables (CV syllables) in refugees with post-traumatic stress disorder (PTSD). PTSD is associated with impaired callosal transfer and with increased right hemisphere activation and impaired executive skills that could influence the processing of dichotic stimuli. A total of 22 participants with PTSD were compared to 23 participants without a diagnosis of PTSD. All participants had similar experiences of acts of war and political violence. They were tested with dichotic listening to CV syllables with free recall and directed attention following the forced attention paradigm. The PTSD group showed increased right ear advantage due to impaired left ear reporting and also smaller attention modulation compared to the control group, and the performance shared variance with self-report measures of arousal and intrusive memories. The results are discussed towards a model of impaired functionality of the frontal lobe and right hemisphere versus impaired callosal transfer, both yielding predictions for the processing of the left ear input and the ability to attention modulation of the performance.
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Affiliation(s)
- Arve E Asbjørnsen
- Bergen Cognition and Learning Group, The University of Bergen, Norway.
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Boggio PS, Rocha M, Oliveira MO, Fecteau S, Cohen RB, Campanhã C, Ferreira-Santos E, Meleiro A, Corchs F, Zaghi S, Pascual-Leone A, Fregni F. Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. J Clin Psychiatry 2010; 71:992-9. [PMID: 20051219 PMCID: PMC3260527 DOI: 10.4088/jcp.08m04638blu] [Citation(s) in RCA: 160] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2008] [Accepted: 03/12/2009] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We aimed to investigate the efficacy of 20 Hz repetitive transcranial magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress disorder (PTSD)-associated symptoms. METHOD In this double-blind, placebo-controlled phase II trial conducted between October 2005 and July 2008, 30 patients with DSM-IV-diagnosed PTSD were randomly assigned to receive 1 of the following treatments: active 20 Hz rTMS of the right DLPFC, active 20 Hz rTMS of the left DLPFC, or sham rTMS. Treatments were administered in 10 daily sessions over 2 weeks. A blinded rater assessed severity of core PTSD symptoms, depression, and anxiety before, during, and after completion of the treatment protocol. In addition, a battery of neuropsychological tests was measured before and after treatment. RESULTS Results show that both active conditions-20 Hz rTMS of left and right DLPFC-induced a significant decrease in PTSD symptoms as indexed by the PTSD Checklist and Treatment Outcome PTSD Scale; however, right rTMS induced a larger effect as compared to left rTMS. In addition, there was a significant improvement of mood after left rTMS and a significant reduction of anxiety following right rTMS. Improvements in PTSD symptoms were long lasting; effects were still significant at the 3-month follow-up. Finally, neuropsychological evaluation showed that active 20 Hz rTMS is not associated with cognitive worsening and is safe for use in patients with PTSD. CONCLUSIONS These results support the notion that modulation of prefrontal cortex can alleviate the core symptoms of PTSD and suggest that high-frequency rTMS of right DLPFC might be the optimal treatment strategy.
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Affiliation(s)
- Paulo Sergio Boggio
- Programa de Pós-Graduação em Distúrbios do Desenvolvimento e Núcleo de Neurociências do Comportamento, Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil
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Pallanti S, Bernardi S. Neurobiology of repeated transcranial magnetic stimulation in the treatment of anxiety: a critical review. Int Clin Psychopharmacol 2009; 24:163-73. [PMID: 19455047 DOI: 10.1097/yic.0b013e32832c2639] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Transcranial magnetic stimulation (TMS) has been applied to a growing number of psychiatric disorders as a neurophysiological probe, a primary brain-mapping tool, and a candidate treatment. Although most investigations have focused on the treatment of major depression, increasing attention has been paid to anxiety disorders. The aim of this study is to summarize published findings about the application of TMS as a putative treatment for anxiety disorders. TMS neurophysiological and mapping findings, both clinical and preclinical, have been included when relevant. We searched Medline, PsycInfo, and the Cochrane Library from 1980 to January 2009 for the terms 'generalized anxiety disorder', 'social anxiety disorder', 'social phobia', 'panic', 'anxiety', or 'posttraumatic stress disorder' in combination with 'TMS', 'cortex excitability', 'rTMS', 'motor threshold', 'motor evoked potential', 'cortical silent period', 'intracortical inhibition', 'neuroimaging', or 'intracortical facilitation'. Most of the therapeutic experiences with repetitive TMS available in the literature are in the form of case reports, not controlled or blinded studies. Stimulation of the right dorsolateral prefrontal cortex, especially at high frequencies, has been reported to reduce anxiety symptoms in posttraumatic stress disorder and panic disorder; nevertheless, results are mixed. A specific role for the right dorsolateral prefrontal cortex in the posttraumatic stress disorder symptom core can be hypothesized. TMS remains an investigational intervention that has not yet gained approval for the clinical treatment of any anxiety disorder. Clinical sham-controlled trials are scarce. Many of these trials have supported the idea that TMS has a significant effect, but in some studies, the effect is small and short lived. The neurobiological correlates suggest possible efficacy for the treatment of social anxiety that still has to be investigated.
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Affiliation(s)
- Stefano Pallanti
- Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY 10029, USA.
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Anxiolytic effects of transcranial magnetic stimulation--an alternative treatment option in anxiety disorders? J Neural Transm (Vienna) 2009; 116:767-75. [PMID: 19137237 DOI: 10.1007/s00702-008-0162-0] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2008] [Accepted: 11/18/2008] [Indexed: 10/21/2022]
Abstract
In contrast to major depression, only few studies are available so far on the effects of repetitive transcranial magnetic stimulation (rTMS) in anxiety disorders. In order to summarise available data concerning the putative anxiolytic action of repetitive rTMS, a systematic literature review was carried out. Although interpretation of the results is difficult because of a large variety of used treatment protocols and the lack of a placebo-controlled design in the majority of studies, there is evidence for anxiolytic action of rTMS both from preclinical trials and studies in humans. Based on the idea of interhemispheric imbalance and/or deficits in cortico-limbic control as a model for human anxiety, inhibitory rTMS of the prefrontal cortex has been shown to exert beneficial effects in a number of studies in healthy subjects, patients with PTSD and panic disorder. However, to further elucidate the putative anxiolytic action of rTMS in patients with anxiety disorders future studies have to be conducted addressing in particular the limitations of the studies mentioned above.
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Osuch EA, Benson BE, Luckenbaugh DA, Geraci M, Post RM, McCann U. Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. J Anxiety Disord 2009; 23:54-9. [PMID: 18455908 PMCID: PMC2693184 DOI: 10.1016/j.janxdis.2008.03.015] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2007] [Revised: 03/18/2008] [Accepted: 03/19/2008] [Indexed: 10/22/2022]
Abstract
Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment-refractory PTSD were studied in a placebo-controlled, crossover design of imaginal exposure therapy with rTMS (1Hz) versus sham. PTSD symptoms, serum and 24h urine were obtained and analyzed. Effect sizes for PTSD symptoms were determined using Cohen's d. Active rTMS showed a larger effect size of improvement for hyperarousal symptoms compared to sham; 24-h urinary norepinephrine and serum T4 increased; serum prolactin decreased. Active rTMS with exposure may have symptomatic and physiological effects. Larger studies are needed to confirm these preliminary findings and verify whether rTMS plus exposure therapy has a role in the treatment of PTSD.
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Affiliation(s)
- Elizabeth A Osuch
- Biological Psychiatry Branch, National Institute of Mental Health, Clinical Center Nursing Department, National Institutes of Health, Bethesda, MD, United States.
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Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder). Brain Stimul 2008; 2:14-21. [PMID: 20633399 DOI: 10.1016/j.brs.2008.06.001] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2008] [Accepted: 06/06/2008] [Indexed: 01/21/2023] Open
Abstract
Brain imaging studies performed over the past 20 years have generated new knowledge about the specific brain regions involved in the brain diseases that have been classically labeled as psychiatric. These include the mood and anxiety disorders, and the schizophrenias. As a natural next step, clinical researchers have investigated whether the minimally invasive brain stimulation technologies (transcranial magnetic stimulation [TMS] or transcranial direct current stimulation [tDCS]) might potentially treat these disorders. In this review, we critically review the research studies that have examined TMS or tDCS as putative treatments for depression, mania, obsessive-complusive disorder, posttraumatic stress disorder, panic disorder, or schizophrenia. (Separate controversy articles deal with using TMS or tDCS to treat pain or tinnitus. We will not review here the large number of studies using TMS or tDCS as research probes to understand disease mechanisms of psychiatric disorders.) Although there is an extensive body of randomized controlled trials showing antidepressant effects of daily prefrontal repetitive TMS, the magnitude or durability of this effect remains controversial. US Food and Drug Administration approval of TMS for depression was recently granted. There is much less data in all other diseases, and therapeutic effects in other psychiatric conditions, if any, are still controversial. Several issues and problems extend across all psychiatric TMS studies, including the optimal method for a sham control, appropriate coil location, best device parameters (intensity, frequency, dosage, and dosing schedule) and refining what subjects should be doing during treatment (activating pathologic circuits or not). In general, TMS or tDCS as a treatment for most psychiatric disorders remains exciting but controversial, other than prefrontal TMS for depression.
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Fitzgerald P. Brain stimulation techniques for the treatment of depression and other psychiatric disorders. Australas Psychiatry 2008; 16:183-90. [PMID: 18568624 DOI: 10.1080/10398560701874291] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The aim of this paper was to review the development of repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagal nerve stimulation (VNS), deep brain stimulation (DBS) and other recent brain stimulation techniques for their potential use in the treatment of a range of psychiatric disorders. CONCLUSIONS A considerable number of studies have been conducted to investigate the efficacy of rTMS. Although there are considerable problems with this research base, globally the studies suggest that rTMS has antidepressant efficacy. However, more research is required to define the most effective way of applying this technique. There is a much smaller research base supporting the use of VNS and to date the research suggests that only a minority of patients benefit from this procedure. Considerably more research is required in the use of the other techniques which at this stage have been tested only to a very small degree. It is likely that one, and possibly a number, of the new brain stimulation techniques will become available clinically in the psychiatric armamentarium in the coming years. However, considerable research is still required to establish efficacy and define the appropriate place in clinical practice for these treatment approaches.
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Affiliation(s)
- Paul Fitzgerald
- Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, VIC, Australia
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Hoffman RE. Auditory/Verbal hallucinations, speech perception neurocircuitry, and the social deafferentation hypothesis. Clin EEG Neurosci 2008; 39:87-90. [PMID: 18450175 DOI: 10.1177/155005940803900213] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Auditory/verbal hallucinations (AVHs) are comprised of spoken conversational speech seeming to arise from specific, nonself speakers. One hertz repetitive transcranial magnetic stimulation (rTMS) reduces excitability in the brain region stimulated. Studies utilizing 1-Hz rTMS delivered to the left temporoparietal cortex, a brain area critical to speech perception, have demonstrated statistically significant improvements in AVHs relative to sham simulation. A novel mechanism of AVHs is proposed whereby dramatic pre-psychotic social withdrawal prompts neuroplastic reorganization by the "social brain" to produce spurious social meaning via hallucinations of conversational speech. Preliminary evidence supporting this hypothesis includes a very high rate of social withdrawal emerging prior to the onset of frank psychosis in patients who develop schizophrenia and AVHs. Moreover, reduced AVHs elicited by temporoparietal 1-Hz rTMS are likely to reflect enhanced long-term depression. Some evidence suggests a loss of long-term depression following experimentally-induced deafferentation. Finally, abnormal cortico-cortical coupling is associated with AVHs and also is a common outcome of deafferentation. Auditory/verbal hallucinations (AVHs) of spoken speech or "voices" are reported by 60-80% of persons with schizophrenia at various times during the course of illness. AVHs are associated with high levels of distress, functional disability, and can lead to violent acts. Among patients with AVHs, these symptoms remain poorly or incompletely responsive to currently available treatments in approximately 25% of cases. For patients with AVHs who do respond to antipsychotic drugs, there is a very high likelihood that these experiences will recur in subsequent episodes. A more precise characterization of underlying pathophysiology may lead to more efficacious treatments.
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Affiliation(s)
- Ralph E Hoffman
- Yale University School of Medicine, New Haven, Connecticut, USA.
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Ipser JC, Pillay NS, Stein DJ, van Honk J. Transcranial magnetic stimulation for post-traumatic stress disorder. Hippokratia 2007. [DOI: 10.1002/14651858.cd006824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Jonathan C Ipser
- University of Stellenbosch; MRC Research Unit for Anxiety and Stress Disorders; PO Box 19063 Tygerberg Western Cape South Africa 7505
| | - Nirvana S Pillay
- University of Cape Town; Department of Psychiatry and Mental Health; 32A Groote Schuur Hospital Anzio Road Cape Town Western Cape South Africa 7925
| | - Dan J Stein
- University of Cape Town; Department of Psychiatry and Mental Health; 32A Groote Schuur Hospital Anzio Road Cape Town Western Cape South Africa 7925
| | - Jack van Honk
- Utrecht University; Psychological Laboratory, Helmholtz Institute; Heidelberglaan 2 Utrecht Netherlands
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