# Proof of concept study to treat negative affect in chronic low back pain

> **NIH NIH UH3** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $745,747

## Abstract

This proposal responds to RFA-NS-19-029 to address the need for better evidence-based pain treatment for
patients with chronic low back pain (CLBP) who have co-occurring negative affective disorders, such as major
depression with anxious features. The CLBP subgroup with comorbid depression or anxiety disorders
(commonly termed, high negative affect) is approximately 20-30% of the 50 million adults with CLBP in this
country. This subgroup is particularly refractory to pain treatment and is in desperate need of better non-
opioid, comprehensive pain treatment options. Patients with CLBP and high levels of negative affect (NA)
suffer higher levels of pain and have worse disability and function. Due to these factors they are prescribed
opioids more frequently and misuse opioids at a much greater rate (40-60% rates of non-adherence), which is
related to self-medication of depression and anxiety by taking extra opioids. Poor pain management in
patients with high NA is due in part to a lack of more effective evidenced-based treatment options to improve
pain, depression, anxiety, and function, and prevent opioid misuse. We have shown in separate RCTs in
CLBP patients with high NA that antidepressants (AD) or “fear avoidance based physical therapy” improve
pain, function, depression, and anxiety. In this proposal we will also present data showing that the combination
of antidepressants + fear avoidance PT is more efficacious than each treatment alone or a control condition.
Moreover, we have also tested an enhanced fear avoidance rehabilitation protocol (EFAR) to improve
outcomes further, and we found it more effective than usual care. To address the unmet needs of CLBP
patients with high negative affect, we propose to test in a randomized trial if the combination of AD+EFAR is
more effective than each treatment alone to improve pain, function, depression, and prevent opioid misuse (3-
arms, in 300 subjects). To better identify responders to components of the intervention (AD or EFAR), we will
use an adaptive design whereby non-responders to each treatment are re-randomized to receive the other
treatment. This multimodal, combination approach of pharmacotherapy +behavioral therapy is novel to the field
and has the potential to shift current treatment paradigms. We will also show that the community practice
environment is poised to make this shift rapidly as well. The primary outcomes are a measure of combined
clinically meaningful changes in pain and self-reported function (Combined Response), and the rate of 50%
improvement in depression symptoms (Depression Response) at 4 months vs. baseline. We track outcomes
for a total of 8 months. The main secondary outcome is the proportion of drug misuse in each treatment group.
Additional secondary outcomes include changes in sleep quality, activity levels, anxiety, craving, and opioid
dose. Our anticipated findings will provide high quality evidence supporting the combined use of AD+EFAR in
the prevalent group o...

## Key facts

- **NIH application ID:** 10216519
- **Project number:** 4UH3AR076568-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** AJAY D WASAN
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $745,747
- **Award type:** 4N
- **Project period:** 2019-09-26 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216519

## Citation

> US National Institutes of Health, RePORTER application 10216519, Proof of concept study to treat negative affect in chronic low back pain (4UH3AR076568-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10216519. Licensed CC0.

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