# Drug interactions involving psychoactive drugs

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $487,078

## Abstract

Commonly-used psychoactive prescription drugs such as opioids, antidepressants, benzodiazepines, and
muscle relaxants are associated with unintentional traumatic injury—a major cause of morbidity, disability, and
death. Given the increasing use of psychoactive prescription drugs, upsurge in persons with multiple chronic
conditions, growth of polypharmacy, and aging of the US population, drug interactions are a major contributor
to psychoactive drug-induced unintentional traumatic injury. Drug interactions cause significant preventable
patient harm and represent a serious public health problem, especially in older adults, since age and
polypharmacy are major risk factors. Known drug interactions are responsible for 13% of evident adverse drug
events (ADEs) and 5% of hospital admissions in older adults, and >25% of community-residing elders will, in
their lifetime, experience a clinically-significant ADE due to an interaction. Further, the risk of drug interactions
is not limited to older adults, as one in four Americans has multiple chronic conditions, which drive
polypharmacy. Therefore, the clinical and public health burden of drug interactions will continue to grow if not
curtailed.
 This project's broad objective is to produce clinically-actionable and biologically-relevant knowledge
about which medications interact with psychoactive prescription drugs to increase the risk of unintentional
traumatic injury, as well as elucidate dose-response effects, duration-response effects, and subgroups most
susceptible to the interactions. We will achieve this objective by: i) conducting high-throughput automated
screening of longitudinal healthcare data to identify potential drug-drug and drug-drug-drug interactions
involving opioids, antidepressants, benzodiazepines, and muscle relaxants that increase the risk of
unintentional traumatic injury; ii) convene a multidisciplinary Expert Panel to review screening results, prioritize
signals for further investigation, and set a priori hypotheses buttressed by putative mechanisms; and iii)
conduct a series of rigorous pharmacoepidemiologic studies to inform causal inferences and thereby generate
clinically-actionable evidence on drug interactions to prevent instances of unintentional traumatic injury.

## Key facts

- **NIH application ID:** 10066303
- **Project number:** 5R01AG060975-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Charles Edward Leonard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $487,078
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066303

## Citation

> US National Institutes of Health, RePORTER application 10066303, Drug interactions involving psychoactive drugs (5R01AG060975-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10066303. Licensed CC0.

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