# Effectiveness, toxicity and safety of opioid and benzodiazepine substitutes

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $355,500

## Abstract

Project Summary/Abstract
In 2016, the Centers for Disease Control and Prevention (CDC) issued guidelines for “all prescribers to avoid
co-prescribing of benzodiazepine (benzo) and opioids”. Other guidelines also advise against benzos for anxiety
because safer substitutes exist (serotonin–norepinephrine reuptake inhibitors [SNRIs] and selective serotonin
reuptake inhibitors [SSRIs]). Since the 2016 CDC guideline, use of gabapentinoids as an opioid substitute has
risen. While recent data showed a decline in opioid prescribing rates after publication of the CDC guideline, a
knowledge gap exists in terms of the rates, effectiveness and safety of opioid/benzo substitute prescribing and
co-prescribing, especially in populations at high risk of drug toxicity: persons living with disabilities, the elderly
and Medicare enrollees in home health care. We now propose to address this gap in knowledge by
comprehensively evaluating the toxicity and effectiveness of opioid and benzo substitutes, alone or in
combination, compared to opioids and benzos. We anticipate the emergence of previously unrecognized
toxicities from drug substitution and co-prescribing. Our Specific Aims are: 1. Assess temporal change in
prescribing rates of opioids, opioid substitutes, benzos and benzo substitutes and their co-prescribing among
commercially insured and Medicare patients, and the role of provider, patient, federal and state policy on drug
substitution and co-prescribing. 2. Examine toxicities (e.g., falls, fractures, emergency room visits) related to
substitutes for opioids and benzos, and how toxicities vary with different combinations of drug substitution and
co-prescribing, using longitudinal data analytic methods as well as data mining methods for previously
unrecognized toxicities. 3. Examine changes in physical function and measures of pain and anxiety in
Medicare enrollees prescribed substitutes for both opioids and benzos, and how these outcomes vary with
different combinations of drug substitution and co-prescribing among Medicare enrollees in home health care.
We will use 20% national Medicare data to identify the elderly and the disabled Medicare populations, and
the Clinformatics Data Mart to identify commercially insured populations. Our overall hypotheses is that the
substitute drugs, alone or in combination, have considerably lower rates of serious toxicity than do opioids and
benzos, with similar effectiveness in many clinical situations. If this is the case, its demonstration by our
proposed research should result in acceleration in the shift away from opioids and benzos to safer alternatives.

## Key facts

- **NIH application ID:** 10199984
- **Project number:** 5R01DA039192-06
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Yong-Fang Kuo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,500
- **Award type:** 5
- **Project period:** 2016-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199984

## Citation

> US National Institutes of Health, RePORTER application 10199984, Effectiveness, toxicity and safety of opioid and benzodiazepine substitutes (5R01DA039192-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10199984. Licensed CC0.

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