Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Thorough consideration of electroconvulsive therapy (ECT) in treatment-resistant psychiatric disorders

To the Editor:

The article by Howes et al. [1] presents a valuable framework and broad access to the topic of treatment-resistant disorders in psychiatry and deserves to be read by both researchers and clinicians. Nevertheless, we would like to comment on the too short and maybe even misleading passage on electroconvulsive therapy (ECT).

The relative importance of ECT for the treatment of the most severe and treatment-resistant disorders in psychiatry and its potential for a better understanding of the neurobiology of treatment response [2, 3] should merit more than only three sentences in an otherwise comprehensive overview. From a practitioner’s viewpoint, ECT is much more than an approved therapy for “treatment-resistant depression and mania” [4]. There is further clear evidence for its effectiveness in schizophrenia [5] and catatonia [6], and ECT is recognized as a standard treatment in guidelines from major psychiatric associations [4].

Beyond this clinical perspective, the authors note that ECT’s mechanism of action is only poorly defined. Not to forget: If we perfectly understood how ECT works, we would as a corollary have perfectly understood the pathophysiology of some of the most impairing psychiatric disorders. Instead of citing recent reviews on mechanisms of action of ECT [7] the authors (hopefully inadvertently) cite a review article from one of the most obvious ideological opponents of ECT, who concludes the abstract of his article by saying that “ECT affects the brain in a similar manner as severe stress or brain trauma”, which obviously is not true [8]. On the contrary, there are several replicated findings that may well represent physiologically relevant factors that are in part associated with, and contribute to, clinical response [9]. Meta-analytic evidence suggests regionally specific brain volume increases, e.g. in the hippocampal region [10]. Moreover, there is corroborative evidence for increased levels of neurotrophic factors after ECT [11] and the reduction of systemic inflammation in the treatment course [12], all factors that correspond well to current hypotheses on depression pathophysiology [13].

To conclude, we think that ECT should be given the consideration it deserves—from both a clinical and scientific perspective—to exploit its full potential for the treatment of severely affected patients, identification of biological markers of treatment response, and the elucidation of the pathophysiology of treatment-resistant psychiatric disorders. For patients with the most serious forms of treatment-resistant mood and psychotic disorders, ECT should be a standard, go-to treatment, not an afterthought.

References

  1. Howes OD, Thase ME, Pillinger T. Treatment resistance in psychiatry: state of the art and new directions. Mol Psychiatry. 2022;27:58–72. https://doi.org/10.1038/s41380-021-01200-3

    Article  PubMed  Google Scholar 

  2. Foo JC, Streit F, Frank J, Witt SH, Treutlein J, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. et al. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy. Am J Med Genet B Neuropsychiatr Genet. 2019;180:35–45. https://doi.org/10.1002/ajmg.b.32700

    Article  PubMed  Google Scholar 

  3. Maffioletti E, Carvalho Silva R, Bortolomasi M, Baune BT, Gennarelli M, Minelli A. Molecular biomarkers of electroconvulsive therapy effects and clinical response: understanding the present to shape the future. Brain Sci. 2021;11:1120. https://doi.org/10.3390/brainsci11091120

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Espinoza RT, Kellner CH. N Engl J Med. 2022;386:667–72. https://doi.org/10.1056/NEJMra2034954

    Article  PubMed  Google Scholar 

  5. Wang G, Zheng W, Li XB, Wang SB, Cai DB, Yang XH, et al. ECT augmentation of clozapine for clozapine-resistant schizophrenia: a meta-analysis of randomized controlled trials. J Psychiatr Res. 2018;105:23–32. https://doi.org/10.1016/j.jpsychires.2018.08.002

    Article  PubMed  Google Scholar 

  6. Lloyd JR, Silverman ER, Kugler JL, Cooper JJ. Electroconvulsive therapy for patients with catatonia: current perspectives. Neuropsychiatr Dis Treat. 2020;16:2191–208.

    CAS  Article  Google Scholar 

  7. Leaver AM, Espinoza R, Wade B, Narr KL. Parsing the network mechanisms of electroconvulsive therapy. Biol Psychiatry. 2021:S0006-3223(21)01796-0. https://doi.org/10.1016/j.biopsych.2021.11.016.

  8. Besse M, Belz M, Folsche T, Vogelgsang J, Methfessel I, Steinacker P, et al. Serum neurofilament light chain (NFL) remains unchanged during electroconvulsive therapy. World J Biol Psychiatry. 2020;21:148–54. https://doi.org/10.1080/15622975.2019.1702717

    Article  PubMed  Google Scholar 

  9. Takamiya A, Plitman E, Chung JK, Chakravarty M, Graff-Guerrero A, Mimura M, et al. Acute and long-term effects of electroconvulsive therapy on human dentate gyrus. Neuropsychopharmacology. 2019;44:1805–11.

    Article  Google Scholar 

  10. Gryglewski G, Lanzenberger R, Silberbauer LR, Pacher D, Kasper S, Rupprecht R, et al. Meta-analysis of brain structural changes after electroconvulsive therapy in depression. Brain Stimul. 2021;14:927–37. https://doi.org/10.1016/j.brs.2021.05.014

    Article  PubMed  Google Scholar 

  11. Pelosof R, Dos Santos LA, Farhat LC, Gattaz WF, Talib L, Brunoni AR BDNF blood levels after electroconvulsive therapy in patients with mood disorders: an updated systematic review and meta-analysis. World J Biol Psychiatry. 2022:1–29. https://doi.org/10.1080/15622975.2022.2058083.

  12. Yrondi A, Sporer M, Péran P, Schmitt L, Arbus C, Sauvaget A. Electroconvulsive therapy, depression, the immune system and inflammation: a systematic review. Brain Stimul. 2018;11:29–51. https://doi.org/10.1016/j.brs.2017.10.013

    Article  PubMed  Google Scholar 

  13. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Prim. 2016;2:16065. https://doi.org/10.1038/nrdp.2016.65

    Article  PubMed  Google Scholar 

Download references

Funding

Open Access funding enabled and organized by Projekt DEAL.

Author information

Authors and Affiliations

Authors

Contributions

DZW drafted the manuscript, CHK and AS revised it critically. All authors approved the final version.

Corresponding author

Correspondence to David Zilles-Wegner.

Ethics declarations

Competing interests

CHK receives royalties from Cambridge University Press for Handbook of ECT, fees from UpToDate for ECT topics, and fees from Northwell Health for teaching in an ECT course.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zilles-Wegner, D., Kellner, C.H. & Sartorius, A. Thorough consideration of electroconvulsive therapy (ECT) in treatment-resistant psychiatric disorders. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01665-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41380-022-01665-w

Search

Quick links