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Other states have developed approaches to minimize opioid- and benzodiazepine-associated risks such as alternate
monitoring systems and/or educating practitioners.27-29
Multiple managed health care organizations have implemented medical electronic alerts as surveillance strategies to
improve medication safety.30,31 Other investigators have suggested that extending default monitoring to the Medicare
population would greatly aid in detection to facilitate individualized care to prevent double threat and triple threat.
Finalization of new CMS policies to prevent opioid overuse
is expected in 2019.23 Expansion of surveillance efforts from
the state to national level may also harmonize state-wide
health care systems and decrease gaps in care coordination.
Review and identification of existing medications should
be undertaken prior to the initiation of a new opioid, benzodiazepine, or muscle relaxant for any patient. This may
involve usage of a PDMP or review of available administrative claims data to detect potentially offending medications.
Within the electronic medical record, an automated alter
would inform the prescriber or their care team of the synergistic risk of adding the agent to the current regimen. For
patients, based on the evidence, that are deemed necessary
for prescribing of a double-threat or triple-threat regimen,
the care plan a priori should feature an automatic monthly
follow-up to ensure successful management of measurable
symptom outcomes and gradual dose reduction or de-prescribing if possible. Confirmation of patient understanding
via pharmacist consultation of treatment goals, potential
risks, adverse events, including availability of opioid overdose reversal agents, must also be built in to the default treatment path. Shared decision making for the medication action
plan and overall care plan will help empower the patient to
state their own treatment goals for these medications and
embolden honest dialogue about benefits and potential risks.
Additional efforts are warranted to ensure that usage of
opioids, benzodiazepines, and muscle relaxants and any concurrent use is clinically necessary. Gradual dose reduction
and de-prescribing protocols have been converted to quality
indicators by organizations such as the Pharmacy Quality
Alliance that are being used by CMS in the Medicare Patient
Safety Reports and in the Medicaid Adult Core Set that
began in 2018. Specifically, CMS has begun to report the
percentage of patients 18 years and above with concurrent
use of prescription opioids and benzodiazepines for 30 or
more cumulative days.32

Limitations
This is a survey-based analysis and thus potentially subject to
reporter error. However, MEPS is a validated database sponsored by the Agency for Health care and Quality of HHS and
is routinely applied for national estimation by researchers and
the federal government for clinical and policy-level decision
making. The analysis endpoint was hospitalization attributable to any cause as the MEPS database does not specify the

Hospital Pharmacy 55(5)
source offending agent. Hence, the association outcome was
all-cause hospitalization. A priori, the study aim was to delineate the increased likelihood of any hospitalization for those
consuming concomitant high-risk medications.

Conclusions
Patients on triple-threat and double-threat experienced a
greater likelihood of hospitalization compared to nonusers. The addition of muscle relaxant to double-threat
users increased hospitalization probability compared to
those on double threat. Amplified national efforts in medication surveillance and data-driven prescribing and follow-up monitoring for concurrent opioid, benzodiazepine,
and muscle relaxant use are needed to reduce this public
health threat.
Acknowledgments
Watanabe receives support from the Health Resources and Services
Administration (HRSA) of the U.S. Department of Health and
Human Services (HHS) under Grant U1WQHP28726, "Geriatrics
Workforce Enhancement Program." Watanabe receives research
support from the State of California Tobacco-Related Disease
Research Program Award Number 588100 and from the National
Academy of Medicine Anniversary Pharmacy Fellowship Program.
He also receives partial support from the National Academy of
Medicine Emerging Leaders in Health and Medicine Scholars program. This information, content, and conclusions are those of the
authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or
the U.S. government, the State of California, or the National
Academies of Sciences, Engineering, and Medicine.

Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD
Jonathan H. Watanabe

https://orcid.org/0000-0002-2543-5305

References
1. CDC Injury Center. Understanding the epidemic. Drug overdose. https://www.cdc.gov/drugoverdose/epidemic/index.html.
Published July 24, 2019. Accessed October 8, 2019.
2. National Institute on Drug Abuse. Overdose death rates. https://
www.drugabuse.gov/related-topics/trends-statistics/overdosedeath-rates. Published January 29, 2019. Accessed September
12, 2019.
3. Rudd RA, Seth P, David F, Scholl L. Increases in drug and
opioid-involved overdose deaths-United States, 2010-2015.
MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452.
doi:10.15585/mmwr.mm655051e1.

https://www.orcid.org/0000-0002-2543-5305 https://www.cdc.gov/drugoverdose/epidemic/index.html https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates

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