OFFICIAL ACTIONS
EEG Biomarkers for Treatment Response Prediction in
Major Depressive Illness
Alik S. Widge, M.D., Ph.D., Carolyn I. Rodriguez, M.D., Ph.D., Linda L. Carpenter, M.D., Ned H. Kalin, M.D.,
William McDonald, M.D., Charles B. Nemeroff, M.D., Ph.D.
At its July 2017 meeting, the APA Board of Trustees voted
to approve a Resource Document developed by the Council
on Research’s Task Force on Biomarkers and Novel Treat-
ments. The Task Force had been charged with evaluating
the evidence for diagnostic and prognostic biomarkers in
the treatment of a range of psychiatric illnesses. The follow-
ing summarizes the Task Force’s report on one biomarker,
quantitative electroencephalography (QEEG).
Major depressive episodes, whether as a major depressive
disorder or occurring as part of another disorder, are a lead-
ing cause of psychiatric disability and economic burden. One
of several contributors to that burden is the uncertainty of
treatment response. Medications, psychotherapies, and so-
matic treatments all are selected based mainly on tolerability.
As a result, many patients undergo multiple therapeutic trials
before obtaining relief and may ultimately receive sub-
optimal treatment. This has spurred great interest in
identifying biomarkers that could aid medication selection
or more quickly terminate an ineffective trial.
QEEG has frequently been suggested as a possible bio-
marker. It effectively measures aspects of cortical function
that may relate to depression, is relatively inexpensive and
quick, and could be performed in an office setting with or-
dinary computers. It remains unclear, however, whether
QEEG has predictive power in major depressive episodes.
Most proposed markers have been studied by single groups.
Recent reviews are highly technical and qualitative, without
practical evidence summaries for the practicing clinician.
The APA Council on Research’s Task Force on Biomarkers
and Novel Treatments thus undertook a quantitative review
and meta-analysis of QEEG in treatment-response prediction
for major depressive episodes.
We screened articles from MEDLINE published in or
before November 2017. Further articles were identified from
the reference lists of published reviews. We retained all ar-
ticles that used QEEG to predict response to a treatment for
a major depressive episode, regardless of patient population,
82 ajp.psychiatryonline.org
treatment, or QEEG analysis. Two independent raters
extracted diagnostic/prediction information from each ar-
ticle and also rated each on three indicators of good research
practice: sample size, correction for multiple statistical test-
ing, and out-of-training-set cross-validation. We entered
diagnostic accuracy into univariate and bivariate random-
effects meta-analyses, including meta-regression for dif-
ferential efficacy of specific biomarkers. A second meta-
regression assessed whether QEEG was more effective at
predicting response to medication, transcranial magnetic
stimulation (rTMS), or other therapies.
We identified 76 articles reporting 81 markers from which
we determined the following meta-analytic estimates of
QEEG’s ability to predict major depressive episode treatment
response: sensitivity50.72 (0.67–0.76); specificity50.68
(0.63–0.73); log(diagnostic odds ratio)51.89 (1.56–2.21); area
under the receiver operator curve50.76 (0.71–0.80). No
single QEEG biomarker or treatment subtype showed greater
predictive power than the all-studies estimate (information
criterion tests on meta-regression). A funnel plot analysis
suggested substantial publication bias in the QEEG litera-
ture, with a lack of small studies reporting null effects. Most
studies did not use ideally rigorous statistical practices.
The Task Force concluded that QEEG is not yet clinically
reliable for predicting depression treatment response. There
is under-reporting of negative results, a lack of out-of-sample
validation in many studies, and a lack of direct replication
of prior findings. Until these limitations are remedied, QEEG
is not recommended for guiding psychiatric treatment
choice.
AUTHOR AND ARTICLE INFORMATION
The full report as approved by the APA Board of Trustees was submitted
to The American Journal of Psychiatry and accepted for publication. It
appears on pp. 44–56 in the January 2019 issue of the Journal (ajp.
psychiatryonline.org/doi/10.1176/appi.ajp.2018.17121358).
Am J Psychiatry 2019; 176:82; doi: 10.1176/appi.ajp.2018.1760101
Am J Psychiatry 176:1, January 2019