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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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). American Psychiatric Pub; 2013.
Richardson LK, Frueh BC, Acierno R. Prevalence estimates of combat-related post-traumatic stress disorder: critical review. Aust N Z J Psychiatry 2010;44:4–19.
Akiki TJ, Abdallah CG. Are There Effective Psychopharmacologic Treatments for PTSD? [Internet]. J Clin Psychiatry. 2018. Available from: https://doi.org/10.4088/jcp.18ac12473.
Grasser LR, Javanbakht A. Treatments of Posttraumatic Stress Disorder in Civilian Populations [Internet]. Curr Psychiatry Rep. 2019. Available from: https://doi.org/10.1007/s11920-019-0994-3.
Reznikov R, Binko M, Nobrega JN, et al. Deep Brain Stimulation in Animal Models of Fear, Anxiety, and Posttraumatic Stress Disorder. Neuropsychopharmacology. 2016;41:2810–2817.
Gouveia FV, Gidyk DC, Giacobbe P, et al. Neuromodulation Strategies in Post-Traumatic Stress Disorder: From Preclinical Models to Clinical Applications. Brain Sci [Internet]. 2019;9. Available from: https://doi.org/10.3390/brainsci9020045.
Langevin J-P, Koek RJ, Schwartz HN, et al. Deep Brain Stimulation of the Basolateral Amygdala for Treatment-Refractory Posttraumatic Stress Disorder. Biol Psychiatry 2016;79:e82–e84.
Van’t Wout M, Longo SM, Reddy MK, et al. Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder. Brain Behav 2017;7:e00681.
Kozel FA, Motes MA, Didehbani N, et al. 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.
Nam D-H, Pae C-U, Chae J-H. Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled Study. Clin Psychopharmacol Neurosci 2013;11:96–102.
Noble LJ, Meruva VB, Hays SA, et al. Vagus nerve stimulation promotes generalization of conditioned fear extinction and reduces anxiety in rats. Brain Stimul 2019;12:9–18.
Peña DF, Childs JE, Willett S, et al. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala. Front Behav Neurosci 2014;8:327.
George MS, Ward HE Jr, Ninan PT, et al. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul 2008;1:112–121.
Rae Olmsted KL, Bartoszek M, Mulvaney S, et al. Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial. JAMA Psychiatry 2019;1–9.
Hanling SR, Hickey A, Lesnik I, et al. Stellate Ganglion Block for the Treatment of Posttraumatic Stress Disorder: A Randomized, Double-Blind, Controlled TrialReg Anesth Pain Med 2016;41:494–500.
Ahmadi N, Moss L, Hauser P, et al. Clinical outcome of maintenance electroconvulsive therapy in comorbid Posttraumatic Stress Disorder and major depressive disorder. J Psychiatr Res 2018;105:132–136.
Kaster TS, Goldbloom DS, Daskalakis ZJ, et al. Electroconvulsive therapy for depression with comorbid borderline personality disorder or post-traumatic stress disorder: A matched retrospective cohort study. Brain Stimul 2018;11:204–212.
Ahmadizadeh MJ, Rezaei M, Fitzgerald PB. Transcranial direct current stimulation (tDCS) for post-traumatic stress disorder (PTSD): A randomized, double-blinded, controlled trial. Brain Res Bull 2019;153:273–278.
Koek RJ, Roach J, Athanasiou N, et al. Neuromodulatory treatments for post-traumatic stress disorder (PTSD). Prog Neuro-Psychopharmacol Biol Psychiatry 2019;92:148–160.
VanElzakker MB, Staples-Bradley LK, Shin LM. The Neurocircuitry of Fear and PTSD [Internet]. Sleep and Combat-Related Post Traumatic Stress Disorder. 2018. p. 111–125. Available from: https://doi.org/10.1007/978-1-4939-7148-0_10.
Fryml LD, Pelic CG, Acierno R, et al. Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. J. ECT [Internet]. 2018; Available from: https://doi.org/10.1097/YCT.0000000000000505.
Isserles M, Shalev AY, Roth Y, et al. Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder--a pilot study. Brain Stimul 2013;6:377–383.
Watts BV, Landon B, Groft A, et al. A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder. Brain Stimul 2012;5:38–43.
Boggio PS, Rocha M, Oliveira MO, et al. Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. J Clin Psychiatry 2010;71:992–999.
Osuch EA, Benson BE, Luckenbaugh DA, et al. Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. J Anxiety Disord 2009;23:54–59.
Cohen H, Kaplan Z, Kotler M, et al. Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Am J Psychiatry 2004;161:515–524.
Kozel FA, Andrew Kozel F, Van Trees K, et al. One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial [Internet]. Psychiatry Research. 2019. p. 153–162. Available from: https://doi.org/10.1016/j.psychres.2019.01.004.
Philip NS, Barredo J, Aiken E, et al. Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. Am J Psychiatry 2019;176:939–948.
van’t Wout-Frank M, Shea MT, Larson VC, et al. Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results. Brain Stimul. [Internet]. 2018; Available from: https://doi.org/10.1016/j.brs.2018.09.011.
Ahmadizadeh, Rezaei. 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.
Carpenter LL, Conelea C, Tyrka AR, et al. 5 Hz Repetitive transcranial magnetic stimulation for posttraumatic stress disorder comorbid with major depressive disorder. J Affect Disord 2018;235:414–420.
Philip NS, Barredo J, van’t Wout-Frank M, et al. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Biol Psychiatry. 2018;83:263–272.
Woodside DB, Colton P, Lam E, et al. Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation treatment of posttraumatic stress disorder in eating disorders: An open-label case series. Int J Eat Disord 2017;50:1231–1234.
Philip NS, Ridout SJ, Albright SE, et al. 5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. J Trauma Stress 2016;29:93–96.
Oznur T, Akarsu S, Celik C, et al. Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? Neurosciences. 2014;19:29–32.
Rosenberg PB, Mehndiratta RB, Mehndiratta YP, et al. Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. J Neuropsychiatr Clin Neurosci 2002;14:270–276.
Hampstead BM, Mascaro N, Schlaefflin S, et al. Variable symptomatic and neurophysiologic response to HD-tDCS in a case series with posttraumatic stress disorder. Int. J. Psychophysiol. [Internet]. 2019; Available from: https://doi.org/10.1016/j.ijpsycho.2019.10.017.
Grisaru N, Amir M, Cohen H, et al. Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a preliminary study. Biol Psychiatry 1998;44:52–55.
Saunders N, Downham R, Turman B, et al. Working memory training with tDCS improves behavioral and neurophysiological symptoms in pilot group with post-traumatic stress disorder (PTSD) and with poor working memory. Neurocase. 2015;21:271–278.
Petrosino NJ, Zandvakili A, Carpenter LL, et al. Pilot Testing of Peak Alpha Frequency Stability During Repetitive Transcranial Magnetic Stimulation. Front Psychiatry 2018;9:605.
Karris BC, Capobianco M. Subconjunctival hemorrhage after high frequency right-sided repetitive transcranial magnetic stimulation. Brain Stimul 2014;7:494–495.
Nakama H, Garcia A, O’Brien K, et al. Case report of a 24-year-old man with resolution of treatment-resistant major depressive disorder and comorbid PTSD using rTMS. J ECT 2014;30:e9–e10.
Tillman GD, Kimbrell TA, Calley CS, et al. Repetitive Transcranial Magnetic Stimulation and Threat Memory: Selective Reduction of Combat Threat Memory P300 Response After Right Frontal-Lobe Stimulation. J Neuropsychiatr 2011;23:40–47.
McCann UD. Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder [Internet]. Archives of General Psychiatry. 1998. p. 276–279. Available from: https://doi.org/10.1001/archpsyc.55.3.276.
Oberman L, Edwards D, Eldaief M, et al. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol 2011;28:67–74.
Gonsalvez I, Baror R, Fried P, et al. Therapeutic Noninvasive Brain Stimulation in Alzheimer’s Disease. Curr Alzheimer Res 2017;14:362–376.
Rossi S, Hallett M, Rossini PM, et al. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009;120:2008–2039.
Reato D, Salvador R, Bikson M, et al. Principles of Transcranial Direct Current Stimulation (tDCS): Introduction to the Biophysics of tDCS [Internet]. Practical Guide to Transcranial Direct Current Stimulation. 2019. p. 45–80. Available from: https://doi.org/10.1007/978-3-319-95948-1_2.
Thair H, Holloway AL, Newport R, et al. Transcranial Direct Current Stimulation (tDCS): A Beginner’s Guide for Design and Implementation [Internet]. Frontiers in Neuroscience. 2017. Available from: https://doi.org/10.3389/fnins.2017.00641.
Dandekar MP, Fenoy AJ, Carvalho AF, et al. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry 2018;23:1094.
Guzzi G, Della Torre A, Chirchiglia D, et al. Critical reappraisal of DBS targeting for movement disorders. J Neurosurg Sci 2016;60:181–188.
Krishnan S, Pisharady KK, Divya KP, et al. Deep brain stimulation for movement disorders. Neurol India 2018;66:S90–S101.
Lozano AM, Hutchison WD, Kalia SK. What Have We Learned About Movement Disorders from Functional Neurosurgery? Annu Rev Neurosci 2017;40:453–477.
Rapinesi C, Kotzalidis GD, Ferracuti S, et al. Brain Stimulation in Obsessive-Compulsive Disorder (OCD): A Systematic Review. Curr Neuropharmacol 2019;17:787–807.
Graat I, Figee M, Denys D. The application of deep brain stimulation in the treatment of psychiatric disorders. Int Rev Psychiatry 2017;29:178–190.
Mallinckrodt CH, Zhang L, Prucka WR, et al. Signal detection and placebo response in schizophrenia: parallels with depression. Psychopharmacol Bull 2010;43:53–72.
Agid O, Siu CO, Potkin SG, et al. Meta-regression analysis of placebo response in antipsychotic trials, 1970-2010. Am J Psychiatry 2013;170:1335–1344.
Rutherford BR, Pott E, Tandler JM, et al. Placebo response in antipsychotic clinical trials: a meta-analysis. JAMA Psychiatry 2014;71:1409–1421.
Mancini M, Wade AG, Perugi G, et al. Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants [Internet]. J Psychiatr Res. 2014. p. 21–29. Available from: https://doi.org/10.1016/j.jpsychires.2014.01.001.
This work was supported in part with funds from the DANA Foundation, Veterans Affairs Canada, and the Harquail Centre for Neuromodulation. The authors declare no conflict of interest related to this work. CH was part of an unrelated advisory board for Medtronic.
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Gouveia, F.V., Davidson, B., Meng, Y. et al. Treating Post-traumatic Stress Disorder with Neuromodulation Therapies: Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, and Deep Brain Stimulation. Neurotherapeutics (2020). https://doi.org/10.1007/s13311-020-00871-0
- Post-traumatic stress disorder (PTSD)
- transcranial magnetic stimulation (TMS)
- transcranial direct current stimulation (tDCS)
- deep brain stimulation (DBS)