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Triple Network Model in Chronic PTSD: Rationale for & Preliminary Efficacy Data on rTMS & Ketamine Novel Combo

activity
post test

Presented by:
Basant Pradhan, MD, FAPA
Professor, Psychiatry & Pediatrics
Founding Program Director, Neuromodulation with Interventional,
Integrative, & Psychedelics (NIP) Fellowship
Cooper University Hospital
Cooper Medical School, Camden, NJ

Faculty Disclosure:

Dr. Pradhan has disclosed that he has no relevant financial relationship(s). No one else in a position to control content has any financial relationships to disclose. Conflict of interest information for the CME Advisory Committee members can be found on the following website: https://cme.ufl.edu/disclosure/. All relevant financial relationships have been mitigated.

Release Date: March 8, 2024
Expiration Date:  March 7, 2026

Target Audience: All physicians

Learning Objectives:

As a result of participation in this activity, participants should be able to:

  1. Enumerate the three brain-circuits involved in the trauma/fear memories of PTSD.
  2. Describe the modulatory role of non-invasive brain stimulation (rTMS) on these brain-circuits.
  3. Describe the mechanism of action of Ketamine in PTSD.
  4. Use the presented information to state the rationale for use of rTMS + Ketamine combo to treat chronic PTSD.

Requirements for successful completion: Certificates are awarded upon successful completion (80% proficiency) of the post-test.

Accreditation: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit: The University of Florida College of Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Resource(s) for further study:

  1. Karam E, Andrews G, Bromet E, et al. The Role of Criterion A2 in the DSM-IV Diagnosis of Posttraumatic Stress Disorder. Biological Psychiatry. 2010;68(5):465-473. https://doi.org/10.1016/j.biopsych.2010.04.032
  2. Milad MR, Pitman RK, Ellis CM, et al. Neurobiological Basis of Failure to Recall Extinction Memory in Posttraumatic Stress Disorder. Biological Psychiatry. 2009; 66(12):1075-1082. https://doi.org/10.1016/j.biopsych.2009.06.026
  3. Fenster RJ, Lebois LAM, Ressler KJ, Suh J. Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man. Nature Reviews Neuroscience. 2018;19:535-551.
  4. Watts BV, Schnurr PP, Mayo L, Young-Xu Y, Weeks WB, Friedman MJ. Meta-Analysis of the Efficacy of Treatments for Posttraumatic Stress Disorder. J Clin Psychiatry. 2013;74(6):e541-e550. doi: 10.4088/JCP.12r0822. https://www.ptsd.va.gov/professional/articles/article-pdf/id41029.pdf
  5. Lancaster CL, Teeters JB, Gros DF, Back SE. Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and Treatment. J Clin Med. 2016;5(11):105. https://doi.org/10.3390/jcm5110105
  6. Watkins LE, Sprang KR, Rothbaum BO. Treating PTSD: A Review of Evidence-Based Psychotherapy Interventions. Front Behav Neurosci. 2018;12. https://doi.org/10.3389/fnbeh.2018.00258
  7. Pradhan B, Gray R, Parikh T, Akkireddi P, Pumariega A. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) as Monotherapy for Chronic PTSD: A Pilot Study. Adolescent Psychiatry. 2015;5(2):125-131(7).
  8. Pradhan B, D’Amico JK, Makani R, Parikh T. Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches. Journal of Trauma & Dissociation. 2016;17(1):35-54. https://doi.org/10.1080/15299732.2015.1046101
  9. Pradhan B, Mitrev L, Moaddell R, Wainer IW, et al. D-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study. Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics. 2018;1866(7):831-839. https://doi.org/10.1016/j.bbapap.2018.03.006
  10. Green CR, Corsi-Travali S, and Neumeister A. The Role of BDNF-TrkB Signaling in the Pathogenesis of PTSD. J Depress Anxiety. 2013;(S4):006. doi: 10.4172/2167-1044.S4-006. PMID: 25226879.
  11. Perez-Benitez CI, Zlotnick C, Stout RI, Lou F, Dyck I, Weisberg R, Keller M. A 5-Year Longitudinal Study of Posttraumatic Stress Disorder in Primary Care Patients. Psychopathology. 2012;45(5):286-293. https://doi.org/10.1159/000331595
  12. Berger W, Mendlowicz MV, Marques-Portella C, et al. Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2009;33(2):169-180. https://doi.org/10.1016/j.pnpbp.2008.12.004
  13. Davidson J, Baldwin D, Stein DJ, et al. Treatment of Posttraumatic Stress Disorder with Venlafaxine Extended Release: A 6-Month Randomized Controlled Trial. Arch Gen Psychiatry. 2006;63(10):1158-1165. doi:10.1001/archpsyc.63.10.1158
  14. Pradhan B & Malik S. Yoga and Mindfulness-Based Cognitive-Behavioral Therapy for Insomnia (Y-MBCT). Sleep Medicine and Mental Health. 2020; https://doi.org/10.1007/978-3-030-44447-1_4
  15. Andrews-Hanna JR, Smallwood J, Spreng RN. The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Ann N Y Acad Sci. 2014;1316(1):29-52. doi:10.1111/nyas.12360
  16. A. Feder, M.K. Parides, J.W. Murrough, A.M. Perez, J. Morgan, S. Saxena,
    K. Kirkwood, M. aan het Rot, K.A.B. Lapidus, L.-B. Wan, D. Losifescu, D.S. Charney, Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial, JAMA Psychiatry 71 (2014) 681–688.
  17. Murrough, J.W., D.V. Iosifescu, L.C. Chang, R.K. Al Jurdi, C.E. Green, A.M. Perez, S. Iqbal, S. Pillemer, A. Foulkes, A. Shah, D.S. Charney, S.J. Mathew, Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial, Am. J. Psychiatry 170 (2013) 1134–1142.
  18. Pradhan B, Mitrev L, Moaddell R, Wainer IW. d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study. Biochim Biophys Acta Proteins Proteom. 2018;1866(7):831-839. doi:10.1016/j.bbapap.2018.03.006
  19. Kan RLD, Zhang BBB, Zhang JJQ, and Kranz GS. Non-invasive brain stimulation for posttraumatic stress disorder: a systematic review and meta-analysis. Translational Psychiatry. 2020;168.
  20. Yan T, Xie Q, Zheng Z, Zou K, Wang L, et al. Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis. Journal of Psychiatric Research. 2017;89:125-135. https://doi.org/10.1016/j.jpsychires.2017.02.021
  21. Belsher BE, Beech EH, Reddy MK, et al. Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. Journal of Psychiatric Research. 2021;138:598-606. https://doi.org/10.1016/j.jpsychires.2021.05.011

If you have any questions please feel free to contact Nancy Boyd at (352) 594-4298 or at nancy.boyd@ufl.edu