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The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression

  • Geriatric Disorders (M Sajatovic and A Aftab, Section Editors)
  • Published:
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Abstract

Purpose of Review

In this review, the efficacy and safety of FDA-approved neuromodulation devices (electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and vagus nerve stimulation (VNS)), as well as emerging neuromodulation treatments currently under investigation.

Recent Findings

ECT is the “gold standard” somatic therapy for treatment-resistant depression (TRD). Although the clinical benefits are outweighed by potential cognitive and cardiovascular side effects in a majority of cases, it remains unfairly stigmatized. TMS has few cognitive or somatic side effects but is not as effective as the treatment of psychotic depression or more treatment-resistant depression in elders. VNS has limited data in older patients but has been shown to be effective in chronic, treatment-resistant adults. Several investigative neuromodulation treatments including magnetic seizure therapy (MST), focal electrically administered seizure therapy (FEAST), transcutaneous VNS (tVNS), transcranial direct current stimulation (tDCS), and deep brain simulation (DBS) shown promise in geriatric TRD.

Summary

ECT, TMS, and VNS are effective treatments for late-life depression, and research has continued to refine the techniques. Investigative neuromodulation techniques are promising, but evidence for the safety and efficacy of these devices in the geriatric population is needed.

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  1. Riva-Posse P, Hermida AP, McDonald WM. The role of electroconvulsive and neuromodulation therapies in the treatment of geriatric depression. Psychiatr Clin North Am. 2013;36(4):607–30.

    PubMed  Google Scholar 

  2. Iriarte IG, George MS. Transcranial magnetic stimulation (TMS) in the elderly. Curr Psychiatry Rep. 2018;20(1):6.

    PubMed  Google Scholar 

  3. McDonald WM, et al. Electroconvulsive therapy and other neuromodulation therapies. In: Schatzberg AF, Nemeroff CB, editors. Textbook of psychopharmacology. Washington DC: Am Psych Press; 2017. p. 861–99.

    Google Scholar 

  4. Group, U.E.R. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003;361(9360):799–808.

    Google Scholar 

  5. Rhebergen D, et al. Older age is associated with rapid remission of depression after electroconvulsive therapy: a latent class growth analysis. Am J Geriatr Psychiatry. 2015;23(3):274–82.

    PubMed  Google Scholar 

  6. Rosen BH, Kung S, Lapid MI. Effect of age on psychiatric rehospitalization rates after electroconvulsive therapy for patients with depression. J Ect. 2016;32(2):93–8.

    PubMed  Google Scholar 

  7. Kellner CH, et al. Right unilateral ultrabrief pulse ECT in geriatric depression: phase 1 of the PRIDE study. Am J Psychiatry. 2016;173(11):1101–9.

    PubMed  PubMed Central  Google Scholar 

  8. Greenberg RM, Kellner CH. Electroconvulsive therapy: a selected review. Am J Geriatr Psychiatry. 2005;13(4):268–81.

    PubMed  Google Scholar 

  9. Andrade C, Arumugham SS, Thirthalli J. Adverse effects of electroconvulsive therapy. Psychiatr Clin North Am. 2016;39(3):513–30.

    PubMed  Google Scholar 

  10. • Nuninga JO, et al. Immediate and long-term effects of bilateral electroconvulsive therapy on cognitive functioning in patients with a depressive disorder. J Affect Disord. 2018;238:659–65 Recent study describing short- and long-term effects of bilateral ECT on cognitive functioning in adults.

    PubMed  Google Scholar 

  11. McClintock SM, et al. Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy. J ect. 2014;30(2):165–76.

    PubMed  PubMed Central  Google Scholar 

  12. Oudega ML, et al. White matter hyperintensities and cognitive impairment during electroconvulsive therapy in severely depressed elderly patients. Am J Geriatr Psychiatry. 2014;22(2):157–66.

    PubMed  Google Scholar 

  13. Kellner CH, et al. Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial. Br J Psychiatry. 2010;196(3):226–34.

    PubMed  PubMed Central  Google Scholar 

  14. O'Connor MK, et al. The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report. Am J Geriatr Psychiatry. 2001;9(4):382–90.

    CAS  PubMed  Google Scholar 

  15. Verwijk E, et al. Short- and long-term neurocognitive functioning after electroconvulsive therapy in depressed elderly: a prospective naturalistic study. Int Psychogeriatr. 2014;26(2):315–24.

    PubMed  Google Scholar 

  16. Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol Psychiatry. 2010;68(6):568–77.

    PubMed  Google Scholar 

  17. Scalia J, et al. Neuropathologic examination after 91 ECT treatments in a 92-year-old woman with late-onset depression. J ect. 2007;23(2):96–8.

    PubMed  Google Scholar 

  18. • Oltedal L, et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy. Biol Psychiatry. 2018;84(8):574–81 Recent study showing neurobiological impact of ECT.

    PubMed  PubMed Central  Google Scholar 

  19. Nuninga, J.O., et al., Volume increase in the dentate gyrus after electroconvulsive therapy in depressed patients as measured with 7T. Mol Psychiatry, 2019. Recent study showing neurobiological impact of ECT in depressed patients.

  20. Abbott CC, et al. Hippocampal structural and functional changes associated with electroconvulsive therapy response. Transl Psychiatry. 2014;4:e483.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Abbott CC, et al. A review of longitudinal electroconvulsive therapy: neuroimaging investigations. J Geriatr Psychiatry Neurol. 2014;27(1):33–46.

    PubMed  Google Scholar 

  22. Bouckaert F, et al. ECT: its brain enabling effects: a review of electroconvulsive therapy-induced structural brain plasticity. J Ect. 2014;30(2):143–51.

    PubMed  Google Scholar 

  23. Fraser LM, O'Carroll RE, Ebmeier KP. The effect of electroconvulsive therapy on autobiographical memory: a systematic review. J Ect. 2008;24(1):10–7.

    PubMed  Google Scholar 

  24. Sigstrom R, et al. Long-term subjective memory after electroconvulsive therapy. BJ Psych Open. 2020;6(2):e26.

    Google Scholar 

  25. McCormick LM, et al. Relative ineffectiveness of ultrabrief right unilateral versus bilateral electroconvulsive therapy in depression. J Ect. 2009;25(4):238–42.

    PubMed  Google Scholar 

  26. Bai S, et al. A computational model of direct brain excitation induced by electroconvulsive therapy: comparison among three conventional electrode placements. Brain Stimul. 2012;5(3):408–21.

    PubMed  Google Scholar 

  27. McDonald WM. Neuromodulation treatments for geriatric mood and cognitive disorders. Am J Geriatr Psychiatry. 2016;24(12):1130–41.

    PubMed  Google Scholar 

  28. McCall WV, et al. Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects. Arch Gen Psychiatry. 2000;57(5):438–44.

    CAS  PubMed  Google Scholar 

  29. Sackeim HA, et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med. 1993;328(12):839–46.

    CAS  PubMed  Google Scholar 

  30. Sackeim H, et al. Seizure threshold in electroconvulsive therapy. Effects of sex, age, electrode placement, and number of treatments. Arch Gen Psychiatry. 1987;44(4):355–60.

    CAS  PubMed  Google Scholar 

  31. Galvez V, et al. Predictors of seizure threshold in right unilateral ultrabrief electroconvulsive therapy: role of concomitant medications and anaesthesia used. Brain Stimul. 2015;8(3):486–92.

    PubMed  Google Scholar 

  32. Sackeim HA, et al. Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimul. 2008;1(2):71–83.

    PubMed  PubMed Central  Google Scholar 

  33. Tor PC, et al. A systematic review and meta-analysis of brief versus ultrabrief right unilateral electroconvulsive therapy for depression. J Clin Psychiatry. 2015;76(9):e1092–8.

    PubMed  Google Scholar 

  34. Kellner CH, et al. A novel strategy for continuation ect in geriatric depression: phase 2 of the PRIDE study. Am J Psychiatry. 2016;173(11):1110–8.

    PubMed  PubMed Central  Google Scholar 

  35. •• Lisanby SH, et al. Neurocognitive effects of combined electroconvulsive therapy (ECT) and venlafaxine in geriatric depression: phase 1 of the PRIDE study. Am J Geriatr Psychiatry. 2020;28(3):304–16 Recent results from landmark study on effect of ECT parameters for geriatric population.

    PubMed  Google Scholar 

  36. Sackeim HA, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. Jama. 2001;285(10):1299–307.

    CAS  PubMed  Google Scholar 

  37. Prudic J, et al. Pharmacological strategies in the prevention of relapse after electroconvulsive therapy. J ect. 2013;29(1):3–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Tew JD, et al. Relapse during continuation pharmacotherapy after acute response to ECT: a comparison of usual care versus protocolized treatment. Ann Clin Psychiatry. 2007;19(1):1–4.

    PubMed  Google Scholar 

  39. Kellner CH, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006;63(12):1337–44.

    PubMed  PubMed Central  Google Scholar 

  40. van Schaik AM, et al. Efficacy and safety of continuation and maintenance electroconvulsive therapy in depressed elderly patients: a systematic review. Am J Geriatr Psychiatry. 2012;20(1):5–17.

    PubMed  Google Scholar 

  41. O'Connor DW, et al. The effectiveness of continuation-maintenance ECT in reducing depressed older patients' hospital re-admissions. J Affect Disord. 2010;120(1):62–6.

    PubMed  Google Scholar 

  42. Petrides G, et al. Continuation and maintenance electroconvulsive therapy for mood disorders: review of the literature. Neuropsychobiology. 2011;64(3):129–40.

    PubMed  PubMed Central  Google Scholar 

  43. Gagne GG Jr, et al. Efficacy of continuation ECT and antidepressant drugs compared to long-term antidepressants alone in depressed patients. Am J Psychiatry. 2000;157(12):1960–5.

    PubMed  Google Scholar 

  44. Berlim MT, et al. Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol Med. 2014;44(2):225–39.

    CAS  PubMed  Google Scholar 

  45. McDonald WM, van Rooij SJH. Targeting PTSD. Am J Psychiatry. 2019;176(11):894–6.

    PubMed  Google Scholar 

  46. • Conelea CA, et al. Transcranial magnetic stimulation for treatment-resistant depression: naturalistic treatment outcomes for younger versus older patients. J Affect Disord. 2017;217:42–7 Recent study on the effect of TMS in depressed younger versus older patients.

    PubMed  PubMed Central  Google Scholar 

  47. O’Connell NE, et al. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018;3:Cd008208.

    PubMed  Google Scholar 

  48. Rossi S, et al. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008–39.

    PubMed  PubMed Central  Google Scholar 

  49. Sabesan P, et al. Transcranial magnetic stimulation for geriatric depression: promises and pitfalls. World J Psychiatry. 2015;5(2):170–81.

    PubMed  PubMed Central  Google Scholar 

  50. Bella R, et al. Clinical presentation and outcome of geriatric depression in subcortical ischemic vascular disease. Gerontology. 2010;56(3):298–302.

    CAS  PubMed  Google Scholar 

  51. Lanza G, et al. Vascular cognitive impairment through the looking glass of transcranial magnetic stimulation. Behav Neurol. 2017;2017:1421326.

    PubMed  PubMed Central  Google Scholar 

  52. Manes F, et al. A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly. Int Psychogeriatr. 2001;13(2):225–31.

    CAS  PubMed  Google Scholar 

  53. Jorge RE, et al. Treatment of vascular depression using repetitive transcranial magnetic stimulation. Arch Gen Psychiatry. 2008;65(3):268–76.

    PubMed  Google Scholar 

  54. Kloppel S, et al. The cortical motor threshold reflects microstructural properties of cerebral white matter. Neuroimage. 2008;40(4):1782–91.

    PubMed  Google Scholar 

  55. Pennisi G, et al. A review of transcranial magnetic stimulation in vascular dementia. Dement Geriatr Cogn Disord. 2011;31(1):71–80.

    PubMed  Google Scholar 

  56. Brodie SM, Borich MR, Boyd LA. Impact of 5-Hz rTMS over the primary sensory cortex is related to white matter volume in individuals with chronic stroke. Eur J Neurosci. 2014;40(9):3405–12.

    PubMed  Google Scholar 

  57. Lisanby SH, et al. 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. 2009;34(2):522–34.

    PubMed  Google Scholar 

  58. Mogg A, et al. A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Psychol Med. 2008;38(3):323–33.

    CAS  PubMed  Google Scholar 

  59. Carreno FR, Frazer A. Vagal nerve stimulation for treatment-resistant depression. Neurotherapeutics. 2017;14(3):716–27.

    PubMed  PubMed Central  Google Scholar 

  60. George MS, et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005;58(5):364–73.

    PubMed  Google Scholar 

  61. • Aaronson ST, et al. A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality. Am J Psychiatry. 2017;174(7):640–8 Recent study on effects of VNS for treatment-resistant depression.

    PubMed  Google Scholar 

  62. Bottomley JM, et al. Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: a systematic review and meta-analysis. Compr Psychiatry. 2019;98:152156.

    PubMed  Google Scholar 

  63. Lisanby SH, et al. Safety and feasibility of magnetic seizure therapy (MST) in major depression: randomized within-subject comparison with electroconvulsive therapy. Neuropsychopharmacology. 2003;28(10):1852–65.

    PubMed  Google Scholar 

  64. Kosel M, et al. Magnetic seizure therapy improves mood in refractory major depression. Neuropsychopharmacology. 2003;28(11):2045–8.

    PubMed  Google Scholar 

  65. Fitzgerald PB, et al. Pilot study of the clinical and cognitive effects of high-frequency magnetic seizure therapy in major depressive disorder. Depress Anxiety. 2013;30(2):129–36.

    PubMed  Google Scholar 

  66. Kayser S, et al. Magnetic seizure therapy of treatment-resistant depression in a patient with bipolar disorder. J ect. 2009;25(2):137–40.

    PubMed  Google Scholar 

  67. Kayser S, et al. Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects. Psychol Med. 2015;45(5):1073–92.

    CAS  PubMed  Google Scholar 

  68. Sahlem GL, et al. Expanded safety and efficacy data for a new method of performing electroconvulsive therapy: focal electrically administered seizure therapy. J ect. 2016;32(3):197–203.

    PubMed  PubMed Central  Google Scholar 

  69. Nahas Z, et al. A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST]. Brain Stimul. 2013;6(3):403–8.

    PubMed  Google Scholar 

  70. Chahine G, et al. Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST). Brain Stimul. 2014;7(3):483–5.

    PubMed  Google Scholar 

  71. Liu J, et al. Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression. J Affect Disord. 2016;205:319–26.

    PubMed  Google Scholar 

  72. • Bretherton B, et al. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation. Aging (Albany NY). 2019;11(14):4836–57 Study on tVNS in elderly population.

    Google Scholar 

  73. Brunoni AR, et al. Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data. Br J Psychiatry. 2016;208(6):522–31.

    PubMed  PubMed Central  Google Scholar 

  74. Shiozawa P, et al. Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. Int J Neuropsychopharmacol. 2014;17(9):1443–52.

    PubMed  Google Scholar 

  75. Jog MV, Wang DJJ, Narr KL. A review of transcranial direct current stimulation (tDCS) for the individualized treatment of depressive symptoms. Pers Med Psychiatry. 2019;17-18:17–22.

    PubMed  Google Scholar 

  76. Shiozawa P, et al. Transcranial direct current stimulation for depression in a 92-year-old patient: a case study. Psychogeriatrics. 2014;14(4):269–70.

    PubMed  Google Scholar 

  77. Galvez V, et al. Neuromodulation therapies for geriatric depression. Curr Psychiatry Rep. 2015;17(7):59.

    PubMed  Google Scholar 

  78. Kisely S, et al. A systematic review and meta-analysis of deep brain stimulation for depression. Depress Anxiety. 2018;35(5):468–80.

    PubMed  Google Scholar 

  79. van Rooij SJH, Holtzheimer PE. Deep brain stimulation for depression: optimism for continued investigation. Clin Pharmacol Ther. 2019;106(4):706–8.

    PubMed  Google Scholar 

  80. Bronstein JM, et al. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011;68(2):165.

    PubMed  Google Scholar 

  81. Philip NS, et al. Theta-burst transcranial magnetic stimulation for posttraumatic stress disorder. Am J Psychiatry. 2019;176(11):939–48.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA

    Sanne J. H. van Rooij PhD, Patricio Riva-Posse MD & William M. McDonald MD

  2. Brain Health Center, Fuqua Center for Late-Life Depression, 12 Executive Park Drive, NE, Floor 5, Atlanta, GA, 30329, USA

    William M. McDonald MD

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  1. Sanne J. H. van Rooij PhD
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  2. Patricio Riva-Posse MD
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  3. William M. McDonald MD
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Correspondence to William M. McDonald MD.

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Conflict of Interest

Dr. van Rooij reports research support by the Brain and Behavior Research Foundation (NARSAD Young Investigator Award). Dr. Riva-Posse has received honoraria from Janssen Pharmaceuticals for serving in a consulting board. Dr. McDonald reports research supported by the National Institute of Neurological Disease and Stroke, National Institute of Aging, Stanley Foundation, Soterix, Neuronetics, NeoSync, and Cervel Neurotherapeutics. He has a contract with Oxford University Press to co-edit a book on the Clinical Guide to Transcranial Magnetic Stimulation in the Treatment of Depression and section editor for Current Psychiatry Reports. He is a consultant for Signant Health. He also receives support from the JB Fuqua Foundation.

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van Rooij, S.J.H., Riva-Posse, P. & McDonald, W.M. The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression. Curr Treat Options Psych 7, 337–348 (2020). https://doi.org/10.1007/s40501-020-00216-w

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