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Rapid Relief of Treatment Resistant Depression by Facilitated Ketamine Infusion: A Preliminary Report

Activitas Nervosa Superior volume 56, pages 28–36 (2014)Cite this article

Abstract

By combining transcranial magnetic stimulation (TMS) with intravenous ketamine therapy, we sought to increase the therapeutic value of TMS and, at the same time, to improve the efficacy of intravenous ketamine therapy among depressed patients previously classified as non-responders. In this preliminary report, we provide evidence for a new and much more reliable method of treating patients with treatment resistant depression. Twenty-eight patients with various degrees of treatment unresponsive depression were treated with a combination of TMS and ketamine infusion. Of these patients, twenty received pretreatment for 3 days to 2 weeks involving intensive (thrice daily) rTMS treatment administered 6 or 7 days/week or priming TMS treatment immediately prior to the combination TMSketamine infusion combination therapy. Eight patients received neither pretreatment nor priming. All of the 28 patients who did fully participate in the first month of treatment experienced relief of psychiatric symptoms, and showed significant psychosocial recovery. In contrast to previous studies examining ketamine or rTMS individually, the positive outcomes presented here suggest a synergistic effect of the combination therapy of TMS and ketamine infusion.

References

  1. Allan, C.L., Herrmann, L.L., & Ebmeier, K.P. (2011). Transcranial magnetic stimulation in the management of mood disorders. Neuropsychobiology, 64, 163–169.

    Article  PubMed  Google Scholar 

  2. Allen, E.A., Pasley, B.N., Duong, T., & Freeman, R.D. (2007). Transcranial magnetic stimulation elicits coupled neural and hemodynamic consequences. Science, 317, 1918–1921.

    Article  PubMed  Google Scholar 

  3. Anderson, B., Mishory, A., Nahas, Z., Borckardt, J.J., Yamanaka, K., Rastogi, K., & George, M.S. (2006). Tolerability and safety of high daily dosese of repetitive transcranial magnetic stimulation in healthy young men. Journal of ECT, 22, 49–53.

    Article  PubMed  Google Scholar 

  4. Bersani, F.S., Minichino, A., Enticott, P.G., Mazzarini, L., Kahn, N., Antonacci, G., Raccah, R.N., Salviati, M., Delle Chiaie, R., Bersani, G., Fitzgerald, P.B., Biondi, M. (2013). Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: A comprehensive review. European Psychiatry, 28, 30–39.

    Article  PubMed  Google Scholar 

  5. Briggs, F., & Usrey, W.M. (2008). Emerging views of corticothalamic function. Current Opinion in Neurobiology, 18, 403–407.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Carpenter, L.L., Janicak, P.G., Aaronson, S.T., Boyadjis, T., Brock, D.G., Cook, I.A., Dunner, D.L., Lanocha, K., Solvason, H.B., Demitrack, M.A. (2012). Transcranial magnetic stimulation (TMS) for major depression: A multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and Anxiety, 29, 587–596.

    Article  PubMed  Google Scholar 

  7. Cazzoli, D., Muri, R.M., Schumacher, R., von Arx, S., Chaves, S., Gutbrod, K., Bohlhalter, S., Bauer, D., Vanbellingen, T., Bertschi, M., Kipfer, S., Rosenthal, C.R., Kennard, C., Bassetti, C.L., Nyffeler, T. (2012). Theta burst stimulation reduces disability during the activities of daily living in spatial neglect. Brain, 135, 3426–3439.

    Article  PubMed  Google Scholar 

  8. Chang, W.H., Kim, Y-H, Bang, O.Y., Kim, S.T., Park, Y.H., & Lee, P.K.W. (2010). Long-term effects of rTMS on motor recovery in patients after subacute stroke. Journal of Rehabilitation Medicine, 42, 758–764.

    Article  PubMed  Google Scholar 

  9. Cusin, C., & Dougherty, D.D. (2012). Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS. Biology of Mood & Anxiety Disorders, 14, 1–9.

    Google Scholar 

  10. Esser, S.K., Hill, S.L., & Tononi, G. (2005). Modeling the effects of transcranial magnetic stimulation on cortical circuits. Journal of Neurophysiology, 94, 622–639.

    Article  PubMed  Google Scholar 

  11. Fava, M., Evins, A.E., & Dorer, D.J. (2003). The problem of the placebo response in clinical trials for psychiatrie disorders: Culprits, possible remedies, and a novel study design approach. Psychotherapy and Psychosomatics, 72, 115–127.

    Article  PubMed  Google Scholar 

  12. Fuggetta, G., & Noh, N.A. (2013). A neurophysiological insight into the potential link between transcranial magnetic stimulation, thalamocortical dysrhythmia, and neuropsychiatrie disorders. Experimental Neurology, 245, 87–95.

    Article  PubMed  Google Scholar 

  13. Gersner, R., Kravetz, E., Feil, J., Pell, G., & Zangen, A. (2011). Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: Differential outcomes in anesthetized and awake animals. Journal of Neuroscience, 31, 7251–7526.

    Article  Google Scholar 

  14. GlobeNewswire. (2012). Brainsway reports positive pivotal multicenter major depression trial results. Retrieved June 25, 2014

    Google Scholar 

  15. Holtzheimer, P.E., & Mayberg, H.S. (2012). Neuromodulation for treatment-resistant depression. ¥100 Medicine Reports, 4, 1–10.

    Google Scholar 

  16. Holtzheimer, P.E., McDonald, W.M., Mufti, M., Kelley, M.E., Quinn, S., Corso, G., & Epstein, C.M. (2010). Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depression and Anxiety, 27, 960–963. ia]Institute of Medicine of the National Academies of Science (2011). Relieving pain in America: A blueprint for transforming prevention, care, education, and research, http://www.iom.edu/relievingpain

    Article  PubMed  PubMed Central  Google Scholar 

  17. Johnson, J.S., Hamidi, M., & Postle, B.R. (2010). Using EEG to explore how rTMS produces its effects on behavior. Brain Topography, 22, 281–293.

    Article  PubMed  Google Scholar 

  18. Lapidus, K.A.B., Soleimani, L., & Murrough, J.W. (2013). Novel glutamatergic drugs for the treatments of mood disorders. Neuropsychiatrie Disease and Treatment, 9, 1101–1112.

    Google Scholar 

  19. Lisanby, S.H., Husain, M.M., Rosenquist, P.B., Maixner, D., Gutierrez, R., Krystal, A., Gilmer, W., Marangell, L.B., Aaronson, S., Daskalakis, Z.J., Canterbury, R., Richelson, E., Sackeim, H.A., George, M.S. (2008). Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: Clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology, 34, 522–534.

    Article  PubMed  Google Scholar 

  20. Liu, C.C., Franaszczuk, P., Crone, N.E., Jouny, C., & Lenz, F.A. (2011). Studies of properties of “pain networks” as predictors of targets of stimulation for treatment of pain. Frontiers in Integrative Neuroscience, 5, 1–7.

    Article  Google Scholar 

  21. Loo, C.K., Alonzo, A., Martin, D., Mitchell, P.B., Galvez, V., & Perminder, S. (2012). Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. British Journal of Psychiatry, 200, 52–59.

    Article  PubMed  Google Scholar 

  22. Lou, H.C., Luber, B., Stanford, A., & Lisanby, S.H. (2010). Self-specific processing in the default network: A single-pulse TMS study. Experimental Brain Research, 207, 27–38.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Massimini, M., Ferrarelli, F., Sarasso, S., & Tononi, G. (2012). Cortical mechanisms of loss of consciousness: Insight from TMS/EEG studies. Archives Italiennes de Biologie, 150, 44–55.

    PubMed  Google Scholar 

  24. Muller, M.B., Toschi, N., Kresse, A.E., Post, A., & Keck, M.E. (2000). Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brains. Neuropsychopharmacology, 23, 205–215.

    Article  PubMed  Google Scholar 

  25. Murrough, J.W., Perez, A.M., Pillemer, S., Stern, J., Parides, M.K., aan het Rot, M., Collins, K.A., Mathew, S.J., Charney, D.S., Iosifescus, D.V. (2013). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biological Psychiatry, 74, 250–256. National Institute of Mental Health. The numbers count: Mental disorders in America. Retrieved June 25, 2014

    Article  PubMed  Google Scholar 

  26. O’Reardon, J.P., Solvason, H.B., Janicak, P.G., Sampson, S., Isenberg, K.E., Nahas, Z., McDonald, W.M., Avery, D., Fitzgerald, P.B., Loo, C., Demitrack, M.A., George, M.S., Sackeim, H.A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62, 1208–1216.

    Article  PubMed  Google Scholar 

  27. Pankevich, D.E., Davis, M., & Altevogt, B.M. (2011). Glutamate-related biomarkers in drug development for disorders of the nervous system: Workshop summary. Washington, DC.

    Google Scholar 

  28. Pascual-Leone, A., Walsh, V., & Rothwell, J. (2000). Transcranial magnetic stimulation in cognitive neuroscience — virtual lesion, chronometry, and functional connectivity. Current Opinion in Neurobiology, 10, 232–237.

    Article  PubMed  Google Scholar 

  29. Preskorn, S.H. (2012). Ketamine: The hopes and the hurdles. Biological Psychiatry, 77, 522–523.

    Article  Google Scholar 

  30. Rossi, S., Cappa, S.F., Babiloni, C., Pasqualetti, P., Miniussi, C., Carducci, F., Babiloni, F., Rossini, P.M. (2001). Prefrontal cortex in long-term memory: an “interference” approach using magnetic stimulation. Nature Neuroscience, 4, 948–952.

    Article  PubMed  Google Scholar 

  31. Rutherford, B.R., & Roose, S.P. (2013). A model of placebo response in antidepressant clinical trials. American Journal of Psychiatry, 170, 723–733.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rutherford, B.R., Rose, S., Sneed, J., & Roose, S.P. (2013). Study design affects participant expectations: A survey. Journal of Clinical Psychopharmacology, 29, 1–6.

    Google Scholar 

  33. Salvadore, G., Cornwell, B.R., Sambataro, F., Latov, D., Colon-Rosario, V., Carver, F., Holroyd, T., DiazGranados, N., Machado-Vieira, R., Grillon, C., Drevets, W.C., Zarate, C.A. (2010). Anterior cingulate desynchronization and functional connectivity with amygdala during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology, 25, 1415–1422.

    Article  Google Scholar 

  34. Sherman, S.M. (2007). Thalamocortical loops and information processing Encyclopedia of pain (pp. 2427–2431).

    Google Scholar 

  35. Sigtermans, M.J., van Hilten, J.J., Bauer, M.C.R., Arbous, M.S., Marinus, J., Sarton, E.Y., & Dahan, A. (2009). Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain, 145, 304–311.

    Article  PubMed  Google Scholar 

  36. Snyder, A.W., Mulcahy, E., Taylor, J.L., Mitchell, D.J., Sachdev, P., & Gandevia, S.C. (2003). Savant-like skills exposed in normal people by suppressing the left fronto-temporal lobe. Journal of Integrative Neuroscience, 2, 149–158.

    Article  PubMed  Google Scholar 

  37. Thut, G., Veniero, D., Romei, V., Miniussi, C., Schyns, P., & Gross, J. (2011). Rhythmic TMS causes local entrainment of natural oscillatory signatures. Current Biology, 21, 1176–1185.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Walter, P. (2011). Transcranial electric stimulation (ES — tDCS; tRNS, tACS) methods. Neuropsychological Rehabilitation: An International Journal, 21, 602–617.

    Article  Google Scholar 

  39. Wang, H-Y, Crupi, D., Liu, J., Stucky, A., Cruciata, G., Di Rocco, A., Friedman, E., Quartarone, A., Ghilardi, M.F. (2011). Repetitive transcranial magnetic stimulation enhances BDNF-TrkB signaling in both brain and lymphocyte. Journal of Neuroscience, 31, 11044–11054.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Warden, D., Rush, A.J., Trivedi, M.H., Fava, M., & Wisniewski, S.R. (2007). The STAR*D project results: A comprehensive review of the findings. Current Psychiatry Reports, 9, 449–459.

    Article  PubMed  Google Scholar 

  41. Young, L., Camprodon, J.A., Hauser, M., Pascual-Leone, A., & Saxe, R. (2010). Disruption of the right temporoparietal junction with transcranial magnetic stimulation reduces the role of beliefs in moral judgements. Proceedings of the National Academy of Sciences of the United States of America, 107, 6753–6758.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. The Neuroscience Center, LLC, Deerfield, IL, USA

    Steven R. Devore Best

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Correspondence to Steven R. Devore Best.

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Devore Best, S.R. Rapid Relief of Treatment Resistant Depression by Facilitated Ketamine Infusion: A Preliminary Report. Act Nerv Super 56, 28–36 (2014). https://doi.org/10.1007/BF03379605

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Key words

  • Treatment-resistant depression
  • Transcranial magnetic stimulation (TMS)
  • Transcranial Electrical Stimulation (tES)
  • NMDA-R antagonist
  • Ketamine infusion
  • Neuromodulation
  • Synergistic effect
  • Remission