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.

  • Matters Arising
  • Published:

Reply to: EEG-based model and antidepressant response

Nature Biotechnology volume 39, pages 28–29 (2021)Cite this article

Subjects

The Original Article was published on 14 December 2020

replying to: G. Nilsonne & F. E. Harrell Jr Nature Biotechnology https://doi.org/10.1038/s41587-020-00768-5 (2020)

Recently, we published a paper reporting a pattern of brain activity as assessed by resting electroencephalography (EEG) that was specifically predictive of outcome with the antidepressant sertraline in comparison to placebo1. In response, Nilsonne and Harrell raise two criticisms in their Matters Arising2: first, that the baseline Hamilton Depression Rating Scale (HAMD17) score was not adjusted for in the treatment outcome and, as a result, the sertraline signature from the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) trial might only be predicting the baseline HAMD17 score and, second, that the EMBARC sertraline signature could only weakly predict the treatment outcome in the second depression dataset. In this reply, we provide a detailed response to address these criticisms, demonstrating that they are inaccurate owing to a misunderstanding of the original analyses or that the claims are not supported by the data. Collectively, we believe that these criticisms do not alter any conclusions in the paper.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Scatterplot of the predicted change in HAMD17 score and the adjusted post-treatment HAMD17 score.

References

  1. Wu, W. et al. An electroencephalographic signature predicts antidepressant response in major depression. Nat. Biotechnol. https://doi.org/10.1038/s41587-019-0397-3 (2020).

  2. Nilsonne, G. & Harrell, F. Jr. EEG-based model and antidepressant response. Nat. Biotechnol. https://doi.org/10.1038/s41587-020-00768-5 (2020).

  3. Chekroud, A. M. et al. Cross-trial prediction of treatment outcome in depression: a machine learning approach. Lancet Psychiatry 3, 243–250 (2016).

    Article  Google Scholar 

  4. De Vries, Y. A. et al. Influence of baseline severity on antidepressant efficacy for anxiety disorders: meta-analysis and meta-regression. Br. J. Psychiatry 208, 515–521 (2016).

    Article  Google Scholar 

  5. Harrell Jr, F. E. & Slaughter, J. C. Biostatistics for Biomedical Research http://hbiostat.org/doc/bbr.pdf (2020).

  6. Bantis, L. Restricted cubic spline. MATLAB Centreal File Exchange. https://www.mathworks.com/matlabcentral/fileexchange/41241-restricted-cubic-spline (2020).

  7. Chandler, G. M. et al. Validation of the Massachusetts General Hospital antidepressant treatment history questionnaire (ATRQ). CNS Neurosci. Therapeutics 16, 322–325 (2020).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

    Wei Wu & Amit Etkin

  2. Wu Tsai Neuroscience Institute, Stanford University, Stanford, CA, USA

    Wei Wu & Amit Etkin

  3. Alto Neuroscience, Inc., Los Altos, CA, USA

    Wei Wu & Amit Etkin

  4. Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA

    Diego A. Pizzagall

  5. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Madhukar H. Trivedi

  6. O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Madhukar H. Trivedi

Authors
  1. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diego A. Pizzagall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madhukar H. Trivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amit Etkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.W. and A.E. contributed to the analysis and interpretation of the data and the drafting and revision of the manuscript. D.A.P. and M.H.T. contributed to the drafting and revision of the manuscript.

Corresponding author

Correspondence to Amit Etkin.

Ethics declarations

Competing interests

W.W. receives salary and equity from Alto Neuroscience. Over the past 3 years, D.A.P. received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Compass Pathway, Otsuka and Takeda Pharmaceuticals as well as an honorarium from Alkermes. In addition, he has received stock options from BlackThorn Therapeutics. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. M.H.T. has served as an adviser or consultant for Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus and Wyeth-Ayerst Laboratories; he has received grants or research support from the Agency for Healthcare Research and Quality, Cyberonics, NARSAD, NIDA and NIMH. A.E. receives salary and equity from Alto Neuroscience and options for equity from Mindstrong Health, Akili Interactive Labs and Sizung for unrelated work.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, W., Pizzagall, D.A., Trivedi, M.H. et al. Reply to: EEG-based model and antidepressant response. Nat Biotechnol 39, 28–29 (2021). https://doi.org/10.1038/s41587-020-0738-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41587-020-0738-2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing