Abstract
Background
Older adults with late-life depression (LLD) often experience incomplete or lack of
response to first-line pharmacotherapy. The treatment of LLD could be improved using
objective biological measures to predict response. Transcranial magnetic stimulation
(TMS) can be used to measure cortical excitability, inhibition, and plasticity, which
have been implicated in LLD pathophysiology and associated with brain stimulation
treatment outcomes in younger adults with depression. TMS measures have not yet been
investigated as predictors of treatment outcomes in LLD or pharmacotherapy outcomes
in adults of any age with depression.
Methods
We assessed whether pretreatment single-pulse and paired-pulse TMS measures, combined
with clinical and demographic measures, predict venlafaxine treatment response in
76 outpatients with LLD. We compared the predictive performance of machine learning
models including or excluding TMS predictors.
Results
Two single-pulse TMS measures predicted venlafaxine response: cortical excitability
(neuronal membrane excitability) and the variability of cortical excitability (dynamic
fluctuations in excitability levels). In cross-validation, models using a combination
of these TMS predictors, clinical markers of treatment resistance, and age classified
patients with 73% ± 11% balanced accuracy (average correct classification rate of
responders and nonresponders; permutation testing, p < .005); these models significantly outperformed (corrected t test, p = .025) models using clinical and demographic predictors alone (60% ± 10% balanced
accuracy).
Conclusions
These preliminary findings suggest that single-pulse TMS measures of cortical excitability
may be useful predictors of response to pharmacotherapy in LLD. Future studies are
needed to confirm these findings and determine whether combining TMS predictors with
other biomarkers further improves the accuracy of predicting LLD treatment outcome.
Keywords
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Article Info
Publication History
Published online: July 22, 2021
Accepted:
July 14,
2021
Received in revised form:
June 16,
2021
Received:
May 20,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
