# An electrophysiological predictor of SSRI response in Veterans with PTSD

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2024 · —

## Abstract

Background and Aims: The costs associated with posttraumatic stress disorder (PTSD) are substantial;
PTSD impacts work productivity, relationship functioning, and physical health, with estimated annual costs to
VA in disability payments of $4.28 billion. Ineffective treatments substantially contribute to the perpetuation of
chronic PTSD symptoms and functional impairment in Veterans and, as a consequence, the enormous public
health burden associated with PTSD. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly
prescribed class of medications for patients with PTSD. However, many patients are not responsive to SSRIs
and there is no rapid, uncomplicated way to determine who will or will not benefit from this family of
medications.
A pre-medication assessment using auditory event-related potentials (ERPs) offers a possible means for
predicting treatment response to SSRIs. More specifically, Loudness Dependence of Auditory Evoked
Potentials (LDAEP), derived from responses to a series of increasingly loud tones, appears to be strongly
influenced by brain serotonin level and thereby holds considerable promise as an indicator of the brain’s
potential responsiveness to SSRIs. The primary aim of the proposed project is to investigate the usefulness of
LDAEP for predicting those individuals who will most likely show a favorable or adverse response to SSRIs. A
secondary aim is to determine LDAEP cut-off values that would enable a clinician to make an individualized
SSRI treatment decision based on a patient’s LDAEP score. A tertiary aim is to evaluate LDAEP as an
objective outcome measure of SSRI response. An exploratory aim will test whether the relationships between
LDAEP and SSRI response differ for men and women and whether men and women have different optimal
LDAEP cut off scores.
Study Design: A sample of 94 Veterans with PTSD (50% male; 50% female) will participate in a 12-week
sertraline trial preceded by a 4-week single-blinded placebo lead-in phase. Embedded in this study are four
assessment sessions: pre-placebo, pre-sertraline, and one and three months after initiating sertraline. The
procedures conducted during each assessment session will be mostly the same. Participants will: a) engage in
the ERP procedure that will yield the LDAEP score, b) complete a battery of symptom outcome measures
including measures of PTSD and depressive symptom severity, c) complete self-report assessments of current
medication use, medication adherence, and side effects, and d) provide a blood sample for measurement of
SSRI level and platelet measurement of serotonin reuptake.
Clinical Implications: Findings from this study may contribute to development of a precision-medicine
approach when choosing an initial psychopharmacological intervention for Veterans with PTSD. Development
of a biological screening method that can be used to identify those individuals who are most likely to be
clinically responsive to an SSRI and those who are more likely t...

## Key facts

- **NIH application ID:** 10909899
- **Project number:** 5I01CX001627-06
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** Suzanne Pineles
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909899

## Citation

> US National Institutes of Health, RePORTER application 10909899, An electrophysiological predictor of SSRI response in Veterans with PTSD (5I01CX001627-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10909899. Licensed CC0.

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