Electroencephalographic biomarkers for treatment response prediction in major depressive illness: A meta-analysis

Alik S Widge, M. Taha Bilge, Rebecca Montana, Weilynn Chang, Carolyn I. Rodriguez, Thilo Deckersbach, Linda L. Carpenter, Ned H. Kalin, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Objective: Reducing unsuccessful treatment trials could improve depression treatment. Quantitative EEG (QEEG) may predict treatment response and is being commercially marketed for this purpose. The authors sought to quantify the reliability of QEEG for response prediction in depressive illness and to identify methodological limitations of the available evidence. Method: The authors conducted a meta-analysis of diagnostic accuracy for QEEG in depressive illness, based on articles published between January 2000 and November 2017. The review included all articles that used QEEG to predict response during a major depressive episode, regardless of patient population, treatment, or QEEG marker. The primary meta-analytic outcome was the accuracy for predicting response to depression treatment, expressed as sensitivity, specificity, and the logarithm of the diagnostic odds ratio. Raters also judged each article on indicators of good research practice. Results: In 76 articles reporting 81 biomarkers, the meta-analytic estimates showed a sensitivity of 0.72 (95% CI= 0.67-0.76) and a specificity of 0.68 (95% CI=0.63-0.73). The logarithm of the diagnostic odds ratio was 1.89 (95% CI= 1.56-2.21), and the area under the receiver operator curve was 0.76 (95% CI=0.71-0.80). No specific QEEG biomarker or specific treatment showed greater predictive power than the all-studies estimate in a meta-regression. Funnel plot analysis suggested substantial publication bias. Most studies did not use ideal practices. Conclusions: QEEG does not appear to be clinically reliable for predicting depression treatment response, as the literature is limited by underreporting of negative results, a lackof out-of-sample validation, and insufficient direct replication of previous findings. Until these limitations are remedied, QEEG is not recommended for guiding selection of psychiatric treatment.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalAmerican Journal of Psychiatry
Issue number1
StatePublished - Jan 2019

Bibliographical note

Funding Information:
Drs. Widge and Deckersbach have pending patent applications related to the use of electrographic markers to characterize patients and select neuromodulation therapies. Dr. Widge has received device donations and consulting income from Medtronic. Dr. Rodriguez has served as a consultant for Allergan, BlackThorn Therapeutics, and Rugen Therapeutics. Dr. Carpenter has served as a consultant for Magstim and has received research clinical trial support from Cervel, Janssen, NeoSync, and Neu-ronetics. Dr. Kalin has received research support from NIMH; he has served as a consultant for CME Outfitters, the Pritzker Neuropsychiatric Disorders Research Consortium, the Skyland Trail Advisory Board, and TC MSO (parent company of Actify Neurotherapies); and he receives remuneration from Elsevier as co-editor of the journal Psychoneuro-endocrinology. Dr. Nemeroff has received grants or research support from NIH and the Stanley Medical Research Institute; he has served as a consultant for Bracket (Clintara), Dainippon Pharma, Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Prismic Pharmaceuticals, Sumitomo Navitor Pharmaceuticals, Sunovion, Taisho Pharmaceutical, Takeda, TC MSO, and Xhale; he has served on scientific advisory boards for the American Foundation for Suicide Prevention (AFSP), the Anxiety Disorders Association of America (ADAA), Bracket (Clintara), the Brain and Behavior Research Foundation, the Laureate Institute for Brain Research, Skyland Trail, and Xhale and on directorial boards for ADAA, AFSP, and Gratitude America; he is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, Corcept Therapeutics, OPKO Health, Seattle Genetics, and Xhale; he receives income or has equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), CME Outfitters, Intra-Cellular Therapies, Magstim, Takeda, and Xhale; and he holds patents on a method and devices for transdermal delivery of lithium (patent 6,375,990B1) and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (patent 7,148,027B2). The other authors report no financial relationships with commercial interests.

Funding Information:
Preparation of this work was supported in part by grants from the Brain and Behavior Research Foundation, the Harvard Brain Science Initiative, and NIH (MH109722, NS100548) to Dr. Widge. The authors further thank Farifteh F. Duffy, Ph.D., and Diana Clarke, Ph.D., of the American Psychiatric Association, for critical administrative and technical assistance throughout preparation.

Publisher Copyright:
© 2019 American Journal of Psychiatry.

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