Preventive Medicine 130 (2020) 105883

Contents lists available at ScienceDirect

Preventive Medicine
journal homepage: www.elsevier.com/locate/ypmed

Prescribing patterns before and after a non-fatal drug overdose using T

Tennessee's controlled substance monitoring database linked to hospital
discharge data
⁎
Shanthi Krishnaswamia, , Sutapa Mukhopadhyaya, Melissa McPheetersa,b, Sarah J. Nechutaa,c
a
Tennessee Department of Health, Office of Informatics and Analytics, 710 James Robertson Parkway, Nashville, TN 37243, United States
b
Departments of Health Policy and Biomedical Informatics, Vanderbilt University Medical Center, 2525 West End Avenue, 408B, Nashville, TN 37203, United States
c
Department of Public Health, Grand Valley State University, 500 Lafayette Ave Northeast, Grand Rapids, MI 49503, United States

A R T I C LE I N FO A B S T R A C T

Keywords: We performed a statewide evaluation of prescribing patterns of controlled substances (CS) before and after an
Emergency department overdose, using Tennessee's Hospital Discharge Data System and the Controlled Substance Monitoring Database
Hospital discharge data (CSMD). Adults' first non-fatal overdose discharges either from the emergency department (ED) or inpatient (IP)
Inpatient hospitalization stay occurring between 2013 and 2016 were linked to prescriptions in the CSMD. The difference in the pro-
Non-fatal drug overdose
portion of patients filling a prescription before versus after an overdose was calculated. Included were 49,398
Opioid overdose
Prescription drug monitoring data
patients with an overdose and a prescription record; most (60.5%) were treated in the ED. Among any drug type
overdose the percentage of patients who filled a CS prescription within a year of experiencing an overdose was as
follows: opioid analgesics: 59.1%, benzodiazepines: 37.3%, stimulants: 5.0%, muscle relaxants: 3.4%, con-
current opioid-benzodiazepines: 24.0% with the percent difference from before to after similar in both settings.
Among patients treated for an opioid overdose, this represented a decrease in opioid analgesics filled by 9.7%
(95%CI: −11.2, −8.3) among those treated in the ED, and by 7.1% (95% CI: −8.3, −5.9) among treated
inpatients. Among patients treated for a heroin overdose, 12.2% (95%CI: −15.2, −9.3) fewer of those treated in
the ED and 8.8% (95%CI: −15.0, −2.7%) fewer of treated inpatients filled a CS prescription in that year. The
most common opioid analgesics included hydrocodone and oxycodone. The number of patients filling bupre-
norphine for treatment increased in the year after overdoses associated with any drug or opioids but decreased
among those treated for a heroin overdose.

1. Introduction Administration, 2018). Despite a decrease in the annual opioid pre-

The United States (U.S.) continues to face a severe epidemic of
opioid-related drug overdoses. National attention on pain management
practices and increasing prevalence of opioid use and misuse in the past
decade have emerged as critical public health challenges. Misuse of
prescription opioids continues to rise, with 11.4 million Americans
estimated to have misused these drugs in 2017. Per the US National
Survey on Drug Use and Health, 0.8% of people had an opioid use
disorder in the period 2015–2017 (Mattson et al., 2017; Han et al.,
2017; Hoots et al., 2018; Substance Abuse and Mental Health Services
Administration, 2017; Substance Abuse and Mental Health Services
scription rate by 19.2% from 2006 to 2017 (Hoots et al., 2018), the
Centers for Disease Control and Prevention (CDC) reported a 30% in-
crease in opioid-related ED overdose visits from July 2016 to September
2017 (Centers for Disease Control and Prevention (CDC), 2018). In
Tennessee (TN), age-adjusted rates for all drug outpatient overdose
visits increased from 46.6 per 100,000 in Q1 2013 to 57.5 per 100,000
in Q4 2016. Rates for outpatient visits for heroin overdose increased
ten-fold during the same period (Tennessee Department of Health,
Office of Informatics and Analytics, 2019).
Non-fatal overdoses are potential opportunities for intervention
(e.g., linkage to treatment, harm reduction such as naloxone, and

Abbreviations: (CDC), Centers for Disease Control and Prevention; (CS), controlled substances; (CSMD), Controlled Substance Monitoring Database; (DOB), date of
birth; (ED), emergency department; (HDDS), Hospital Discharge Data System; (IP), inpatient; (ICD-9-CM), International Classification of Diseases, Ninth Revision,
Clinical Modification; (ICD-10-CM), International Classification of Diseases, 10th Revision, Clinical Modification; (LA), long-acting; (MAT), medication-assisted
treatment; (PDMP), Prescription Drug Monitoring Program; Short-acting, (SA); (TN), Tennessee; (TDH), Tennessee Department of Health
⁎
Corresponding author at: Andrew Johnson Tower, 7th Floor, 710 James Robertson Parkway, Nashville, TN 37243, United States.
E-mail address: Shanthi.Krishnaswami@tn.gov (S. Krishnaswami).

https://doi.org/10.1016/j.ypmed.2019.105883
Received 15 June 2019; Received in revised form 4 October 2019; Accepted 4 November 2019
Available online 06 November 2019
0091-7435/ © 2019 Elsevier Inc. All rights reserved.
S. Krishnaswami, et al.
follow-up care) to reduce subsequent opioid-related morbidity or
mortality (Hoots et al., 2018; Cochran et al., 2017; Darke et al., 2007).
Existing literature on overdose largely focuses either on fatal overdose
or on the drugs present at the time of overdose, but typically does not
address prescribing patterns before and after a non-fatal overdose. Al-
though Frazier et al. (2017), evaluated prescription use six months
before and after an overdose among Pennsylvania Medicaid enrollees
using data through 2013, they evaluated only opioid prescriptions in a
combined sample of inpatient and outpatient non-fatal opioid over-
doses and did not account for other controlled substances or other payer
populations.
Opioid prescribing is a well-established risk factor for future opioid
use disorder or overdose (Larochelle et al., 2016; Darke et al., 2007;
Liang and Turner, 2015; Dilokthornsakul et al., 2016; Dunn et al., 2010;
Saha et al., 2016). Individuals treated for chronic pain may be at higher
risk due to co-prescribing of multiple medications (Jones and
McAninch, 2015; Sun et al., 2017; Park et al., 2015; Hernandez et al.,
2018; Geissert et al., 2018; Okumura et al., 2017; Okumura and Nishi,
2017) and medication types. Theoretically, experiencing a health event
such as an overdose could change future health practices, including
prescriptions. As state-level policy continues to have a strong focus on
managing prescribing patterns, it is important to describe these patterns
to guide policy and program decisions. We conducted this study in
Tennessee, which continues to be one of the highest prescribing states
and one with very high overdose rates.
This is the first study linking data in TN on non-fatal overdoses with
prescribing patterns before and after the events, using the Hospital
Discharge Data System (HDDS) and the state's Prescription Drug
Monitoring Program (PDMP), the Controlled Substance Monitoring
Database (CSMD). The study focused on adults ≥18 years old with their
first non-fatal overdose during 2013–2016. We evaluated the pre-
scribing patterns for opioid analgesics, opioids for medication assisted
treatment (MAT), benzodiazepines, and other CS 90 and 365 days be-
fore and after an ED visit or inpatient (IP) hospitalization for a drug
overdose. We looked at prescribing patterns separately in the ED and in
the hospital because patients treated in one versus the other may have
important differences (Jeffery et al., 2018), including a typically older
population treated inpatient and a higher rate of co-prescribing for
comorbid conditions in this group. Due to differing risks associated with
long vs. short acting preparations, we examined different drug types
associated with each overdose. This study captures information on all
CS filled regardless of payment type (including cash) for drug overdoses
overall, opioid overdoses and heroin-specific overdoses.
2. Methods
2.1. Data sources
2.1.1. Hospital discharge data (1/2013–12/2016)
TN HDDS data includes both inpatient (IP) and outpatient claims
data following Uniform billing (UB04) standards from TN hospitals,
including acute care, rehabilitation, and veteran's administration hos-
pitals (Tennessee Department of Health, Office of Healthcare Statistics,
2017). On October 1st, 2015, hospitals implemented a transition from
International Classification of Diseases (ICD), Ninth Revision, Clinical
Modification (ICD-9-CM) diagnosis coding to ICD-10-CM diagnosis
coding. All hospitals licensed by the Tennessee department of health
(TDH) are required by law to report every inpatient and outpatient
discharge to the Department of Health quarterly.
2.1.2. Controlled Substance Monitoring Database (CSMD: 1/2012–12/
2017)
TDH established the CSMD to monitor the dispensing of Schedule II,
III, IV & V CS on December 1 2006. The prescription data is collected
routinely and dispensers report all controlled substances dispensed
within one business day, with the exception of veterinarians who report
2
Preventive Medicine 130 (2020) 105883
within 14 days. This reporting schedule went into effect in the TN
Prescription Safety Act of 2016. The CSMD includes information on
patients, such as name, address, date of birth (DOB), and sex.
Prescription data collected includes drug quantity, national drug code
number (NDC), days' supply, date filled, payment type, sex, number of
refills, number of authorized refills, provider DEA number, and dis-
penser DEA number. We link prescription data via NDC to the CDC
conversion Reference Table (National Center for Injury Prevention and
Control, 2016), providing drug class, drug type, product and generic
name, dosage, and form data and enhance the use of the CSMD data by
using comprehensive cleaning and standardization procedures for each
data item (Golladay and Nechuta, 2018). We applied standardized
geocoding methods to clean addresses in both datasets (address match
score of ≥85 and a spelling sensitivity of 80 using address points) with
ArcGIS, version10.6 (ESRI, Redlands, CA, USA).
2.2. Study population
We included TN residents ≥18 years visiting an acute care hospital
with a first non-fatal overdose (ED visit or IP hospitalization) between
January 1st 2013 and December 31st 2016 in this retrospective cohort
study. The first non-fatal overdose refers to the first overdose occurring
during the study period and resulting in ED visit or hospitalization. We
excluded those who died during the visit. We considered all drug, as
well as opioid and heroin-specific non-fatal overdoses in this analysis.
Overdoses related to any drug type are important because polydrug
prevalence is high and many include an opioid. In addition, opioid
overdoses specifically have been a focus of policy practice in Tennessee
and heroin overdoses have been rising steadily. Definitions for drug
overdoses (Web Appendix A) are based on guidelines from the CDC
Toolkit 3.0 developed for use by the Prevention for the States/Data-
Driven Prevention Initiative Programs (CDC's Opioid Overdose
Indicator Support Toolkit, 2018). HDDS has up to 18 fields providing
diagnostic codes and up to three fields for external cause of injury
codes. Only intentional (suicide), unintentional, assault and un-
determined intent codes along with initial and missing encounters were
included. For the ICD-9 period, relevant diagnosis codes were searched
in the primary diagnosis field along with any mention of the specific
external cause of injury codes while for the ICD-10 period, relevant
diagnosis codes were searched in any of the 18 diagnosis fields.
2.3. Cohort creation
Details on our data linkage approach for TN's PDMP data have been
previously published (Nechuta et al., 2019). Briefly, we used names and
date of birth as our primary linkage variables, which are cleaned and
standardized in both the PDMP and HDDS data. We applied fuzzy/
probabilistic matching in SAS Data Management Studio Software v 2.7
(SAS Institute Inc., 2016) using sensitivity values of 85 for names and
85 for DOB. We implemented a systematic approach to identify false
positive matches (both in the HDDS data as part of de-duplication of
overdose records and in the linked overdose patient records to the
CSMD data) that included manual review and use of additional iden-
tifying information that is available for a subset of records (e.g., geo-
coded address, social security number) to exclude false positive mat-
ches.
2.4. Analytic sample
We excluded data items with missing first or last names, DOB before
1900, non-human patient records, missing prescription fill dates and
zero or missing days' supply or quantity. We identified 82,963 ED and
IP overdose visits during 2013–2016 in the HDDS data for an initial
eligible sample for linkage of 54,827 patients with first overdose. After
linkage, we excluded 954 patients who were identified as false positive
matches for a final sample of 49,398 patients for analysis (Web
S. Krishnaswami, et al. Preventive Medicine 130 (2020) 105883

Table 1
Distribution of demographic characteristics among adult subjects discharged after first non-fatal drug overdose visit, TN HDDS 2013–2016 (n = 49,398).
Emergency department visits Inpatient stays

All drug Opioid Heroin All drug Opioid Heroin

(n = 29,880) (n = 4246) (n = 1666) (n = 19,518) (n = 4816) (n = 385)

n (%) n (%) n (%) n (%) n (%) n (%)

Age
Mean ± SD 42.6 ± 17.45 44.6 ± 16.91 32.5 ± 10.18 50.2 ± 17.28 52.9 ± 15.69 34.2 ± 11.26
18–24 years 5053 (16.9) 517 (12.2) 370 (22.2) 1519 (7.8) 183 (3.8) 85 (22.1)
25–34 years 6813 (22.8) 946 (22.3) 763 (45.8) 2739 (14.0) 545 (11.3) 154 (40.0)
35–44 years 5457 (18.3) 750 (17.7) 308 (18.5) 3049 (15.6) 652 (13.5) 67 (17.4)
45–54 years 5104 (17.1) 801 (18.9) 137 (8.2) 4142 (21.2) 1078 (22.4) 49 (12.7)
55–64 years 3665 (12.3) 644 (15.2) 77 (4.6) 3912 (20.0) 1245 (25.9) 25 (6.5)
65–74 years 2122 (7.1) 370 (8.7) 11 (0.7) 2443 (12.5) 711 (14.8) 5 (1.3)
75–84 years 1220 (4.1) 161 (3.8) 1244 (6.4) 309 (6.4)
85+ years 446 (1.5) 57 (1.3) 470 (2.4) 93 (1.9)

Race
White 25,368 (85.4) 3812 (90.2) 1525 (92.3) 16,956 (87.5) 4423 (92.4) 344 (89.6)
Black 3883 (13.1) 364 (8.6) 104 (6.3) 2215 (11.4) 329 (6.9) 35 (9.1)
Other 461 (1.6) 50 (1.2) 23 (1.4) 215 (1.1) 35 (0.7) 5 (1.3)
Unknown 168 20 14 132 29 1

Sex
Female 17,631 (59.0) 2305 (54.3) 600 (36.0) 11,569 (59.3) 2876 (59.7) 132 (34.3)
Male 12,247 (41.0) 1941 (45.7) 1065 (64.0) 7949 (40.7) 1940 (40.3) 253 (65.7)
Unknown 2 1

NCHS- region
Non-metro 8647 (28.9) 1275 (30.0) 89 (5.3) 4770 (24.4) 1259 (26.2) 30 (7.8)
Metro 21,231 (71.1) 2971 (70.0) 1576 (94.7) 14,746 (75.6) 3555 (73.8) 355 (92.2)
Missing 2 1 2 2

Comorbid conditions
Hypertension without complication 6745 (22.6) 1071 (25.2) 128 (7.7) 7699 (39.4) 1978 (41.1) 72 (18.7)
Diabetes 2432 (8.1) 282 (6.6) 19 (1.1) 2810 (14.4) 682 (14.2) 17 (4.4)
Renal disease 536 (1.8) 100 (2.4) 5 (0.3) 1913 (9.8) 514 (10.7) 6 (1.6)
Rheumatologic disease 294 (1.0) 72 (1.7) 5 (0.3) 564 (2.9) 201 (4.2) 4 (1.0)
Alcohol abuse 2828 (9.5) 318 (7.5) 118 (7.1) 3105 (15.9) 558 (11.6) 87 (22.6)
Drug abuse 5822 (19.5) 1078 (25.4) 638 (38.3) 6218 (31.9) 1733 (36.0) 285 (74.0)
Psychoses 1148 (3.8) 112 (2.6) 12 (0.7) 1096 (5.6) 155 (3.2) 10 (2.6)
Depression 7552 (25.3) 823 (19.4) 85 (5.1) 7206 (36.9) 1500 (31.1) 81 (21.0)
Cancer 171 (0.6) 52 (1.2) 0 (0) 515 (2.6) 169 (3.5) 1 (0.3)

NCHS=National Center for Health Statistics; TN = Tennessee; HDDS=Hospital Discharge Data System.

Appendix B).
2.5. CSMD prescription history
We first identified all prescriptions filled in the CSMD in the year
before and after a non-fatal overdose event. Next, binary variables were
created both for the drug class (opioids, benzodiazepine, stimulants and
muscle relaxants) and available specific drug types including opioids
for pain, buprenorphine for MAT (methadone for MAT is not collected
in the CSMD), methadone for pain, hydrocodone short acting (SA),
oxycodone (SA/long acting (LA), oxymorphone LA, tramadol SA, co-
deine, morphine (LA/SA), fentanyl (LA/SA), alprazolam, clonazepam,
diazepam and lorazepam). We grouped payment type cash, Medicare,
Medicaid and other. We included a measure of overlapping prescrip-
tions defined as having a prescription for both an opioid and benzo-
diazepine that overlapped by at least two days.
2.6. Patient characteristics
We used HDDS data for the following: 1) age, categorized in years
(18–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84, 85+); 2) race
(white, black, other, missing), and 3) sex (female, male, missing). We
also created the National Center for Health Statistics 2013 Urban-Rural
classification scheme (large, medium, small metropolitan vs. non-me-
tropolitan categories) for counties using county of patient residence
(Ingram and Franco, 2014). We used ICD-9-CM and ICD-10-CM
diagnostic codes based on algorithms described by Quan et al. (2005),
to identify major health conditions in the overdose population, in-
cluding hypertension without complication, diabetes, renal disease,
rheumatologic disease, alcohol abuse, drug abuse, psychoses, depres-
sion and cancer. Demographic and comorbid conditions were selected
based on literature showing association with drug overdose (Peterson
et al., 2019; Hasegawa et al., 2014; Olfson et al., 2018; Yokell et al.,
2014; Elzey et al., 2016; Man et al., 2004; Unick and Ciccarone, 2017;
Meiman et al., 2015; Jiang et al., 2017). Only comorbid conditions that
existed at the time of admission or identified while receiving treatment
for an overdose in the ED or during hospital stay were captured.
2.7. Statistical analyses
Descriptive statistics (frequency and proportions) were calculated
for the basic demographic and clinical (comorbidity) characteristics by
type of overdose event (all drug, opioid and heroin overdose) from both
ED and IP overdoses. Next, prescription variables for two time-frames
(filled 90 and 365 days before and after the first overdose) were com-
puted for each type of overdose outcome. The difference in the pro-
portion of patients filling a prescription from before to after overdose,
along with 95% confidence intervals (CIs) were calculated using gen-
eralized estimating equations in logistic regression models. As all ana-
lyses for methadone for pain were based on < 1% prevalence, we ex-
cluded this drug type from further analyses. All analyses were
conducted using SAS v 9.4 (SAS Institute, Cary, NC) with results shown

3
S. Krishnaswami, et al. Preventive Medicine 130 (2020) 105883

at the patient level. TDH Institutional Review Board approval was ob- MAT increased after overdose, although the changes were negligible
tained for the present analysis. (difference (95% CI): ED: 0.5% (0.2%, 0.8%), hospital: 0.5% (0.3%,
0.9%)). We observed a similar percent difference in the dispensing
3. Results pattern of CS in the 90 day period.

There were 49, 398 TN residents aged ≥18 years who experienced
68,021 discharges with a drug overdose event and at least one pre-
scription record. This included 29,880 drug overdose ED visits (60.5%)
and 19,518 (39.5%) overdose IP hospitalizations. Prescription opioid
was involved in 14.2% of the ED visits and about 25% of the IP stays
while heroin was involved in 5.6% of the ED visits and 2.0% of the IP
overdose stays.
3.1. Demographic factors (Table 1)
Across types of overdose (all drug, opioid, heroin), those discharged
from the ED were younger than individuals with inpatient hospitali-
zations. Among those with overdose of any type, race was similar
among ED and inpatients (White: 85.4% vs. 87.5%) as was gender
(females: 59%). There were fewer comorbid conditions identified
among ED than IP overdose discharges. Individuals treated in an ED for
an opioid overdose were less likely to be females, whites, metro re-
sidents and have comorbid conditions (drug abuse, hypertension
without complications, depression). ED heroin overdose discharges had
lower proportions of patients with substance use or depression com-
pared to inpatients and this may be due to regulations under 42 CFR.
3.2. Prescriptions before and after drug overdoses of any type (Table 2)
Among the population experiencing an overdose, the proportion
filling a controlled substance prescription decreased after an overdose
for all CS prescription types, regardless of overdose setting (ED or IP) or
timing of the prescription use (i.e., within 365 days or 90 days of
overdose). The largest decrease was observed for opioid analgesics,
with a reduction of 6% after an overdose treated in the ED (95% CI
difference: −6.5%, −5.3%), followed by benzodiazepines (3.6% de-
crease, 95% CI: −4.2%, −3.2%), and stimulant and muscle relaxants
(≤ 2% decrease). A similar pattern was observed among those hospi-
talized for all drug overdoses. The percentage of patients with an
overlapping opioid and benzodiazepine prescription decreased by 3.6%
among overdoses treated in the ED and 4.8% among drug overdoses
treated in the inpatient setting. The utilization of buprenorphine for
3.3. Prescriptions filled before and after opioid overdose (Table 3)
In the year before an opioid overdose treated in the ED, 3353 pa-
tients (79.0%) had filled an opioid analgesic, 1946 (45.8%) filled a
benzodiazepine, about 7% filled an opioid for MAT and 38.2% filled a
concurrent prescription. Before an opioid overdose treated as an in-
patient, 4155 (86.3%) filled an opioid analgesic, 2847 (59.1%) a ben-
zodiazepine, 4.2% filled MAT opioid and 53% filled a concurrent pre-
scription. In the year after opioid overdose, decreases in the proportion
of patients filling CS were between one and 4% for all drug categories
except opioids for pain which decreased by 9.7% (95% CI: −11.2%,
−8.3%). The percentage of patients filling buprenorphine for MAT
after overdose increased by 1.3% (95% CI: 0.5%, 2.0%)) among those
who were treated in the ED and by 0.9% (95% CI: 0.2%, 1.5%) among
IP overdoses. The proportion of patients who filled overlapping pre-
scriptions decreased after opioid overdose regardless of treatment set-
ting.
3.4. Prescriptions before and after heroin overdose (Table 4)
Among patients treated in the ED for a heroin overdose, the pro-
portion who still filled a controlled substance in the following year
decreased in most drug categories, with a 12.2% (95% CI: −15.2%,
−9.3%) reduction for opioid analgesics, 4.6% (95% CI: −6.5%,
−2.7%) for benzodiazepines and 3.2% (95% CI: −4.6%, −1.9%) for
overlapping opioid and benzodiazepine prescriptions. The utilization of
stimulant and muscle relaxant prescriptions showed a minimal reduc-
tion (1 to 2%) while buprenorphine for MAT showed almost no change.
We also observed a decrease in the number of patients filling a pre-
scription in the year after a hospital stay for heroin overdose.
3.5. Prescriptions filled by drug type (Figs. 1 and 2)
Patients who were treated in the ED for a drug overdose of any type
frequently filled codeine (47.6%) followed by oxycodone LA (30.2%)
and morphine (19.7%) in the year before overdose while hydrocodone
SA (53.6% vs. 35.8%) and oxycodone SA (45.5% vs. 23.2%) were the

Table 2
Change in opioid, benzodiazepine, and stimulant prescribing before and after the first non-fatal all drug overdose (TN HDDS: 2013–2016, CSMD: 2012–2017).
Emergency department visits (n = 29,880) Inpatient stays (n = 19,518)

Before n (%) After n (%) Differencea (95% CI) Before n (%) After n (%) Differencea (95% CI)

365 days before and after first non-fatal overdose

Any prescription 23,384 (78.3) 21,943 (73.4) −4.9 (−5.4, −4.3) 16,321 (83.6) 15,563 (79.7) −3.9 (−4.5, −3.3)
Opioid for pain 19,431 (65.0) 17,666 (59.1) −5.9 (−6.5, −5.3) 14,239 (73.0) 13,266 (68.0) −5.0 (−5.7, −4.3)
Benzodiazepine 12,231 (40.9) 11,138 (37.3) −3.6 (−4.2, −3.2) 9917 (50.8) 9147 (46.9) −3.9 (−4.6, −3.3)
Buprenorphine for MAT 1575 (5.3) 1722 (5.8) 0.5 (0.2, 0.8) 851 (4.4) 962 (4.9) 0.5 (0.3, 0.9)
Stimulant 1734 (5.8) 1502 (5.0) −0.8 (−1.0, −0.6) 810 (4.2) 724 (3.7) −0.5 (−0.7, −0.2)
Muscle relaxant 1488 (5.0) 1017 (3.4) −1.6 (−1.8, −1.4) 1288 (6.6) 828 (4.2) −2.4 (−2.6, −2.1)
Concurrent opioid and benzodiazepine 8238 (27.6) 7164 (24.0) −3.6 (−4.0, −3.2) 7663 (39.3) 6725 (34.5) −4.8 (−5.4, −4.2)

90 days before and after first non-fatal overdose

Any prescription 18,056 (60.4) 16,425 (55.0) −5.4 (−6.0, −4.9) 13,653 (70.0) 12,818 (65.7) −4.3 (−4.9, −3.6)
Opioid for pain 13,133 (44.0) 11,572 (38.7) −5.3 (−5.8, −4.7) 10,888 (55.8) 10,006 (51.3) −4.5 (−5.2, −3.9)
Benzodiazepine 9746 (32.6) 8605 (28.8) −3.8 (−4.2, −3.4) 8189 (42.0) 7366 (37.7) −4.3 (−4.8, −3.6)
Buprenorphine for MAT 927 (3.1) 1006 (3.4) 0.3 (0.1, 0.4) 508 (2.6) 588 (3.0) 0.4 (0.2, 0.6)
Stimulant 1264 (4.2) 1090 (3.6) −0.6 (−0.7, −0.4) 601 (3.1) 507 (2.6) −0.5 (−0.7, −0.3)
Muscle relaxant 976 (3.3) 753 (2.5) −0.8 (−0.9, −0.6) 809 (4.1) 619 (3.2) −0.9 (−1.2, −0.8)
Concurrent opioid and benzodiazepine 5924 (19.8) 4983 (16.7) −3.1 (−3.5, −2.8) 5877 (30.1) 5025 (25.8) −4.3 (−4.9, −3.8)

MAT = medication assisted treatment; TN = Tennessee; HDDS=Hospital Discharge Data System; CSMD = Controlled Substance Monitoring Database.
a
= % difference.

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S. Krishnaswami, et al. Preventive Medicine 130 (2020) 105883

Table 3
Change in opioid, benzodiazepine, and stimulant prescribing before and after the first non-fatal, opioid (non-heroin) drug overdose TN HDDS: 2013–2016, CSMD:
2012–2017).
Emergency department visits (n = 4246) Inpatient stays (n = 4816)

Before n (%) After n (%) Differencea (95% CI) Before n (%) After n (%) Differencea (95% CI)

365 days before and after first non-fatal overdose

Any prescription 3654 (86.1) 3351 (78.9) −7.1 (−8.5, −5.8) 4383 (91.0) 4166 (86.5) −5.0 (−5.5, −3.5)
Opioid for pain 3353 (79.0) 2941 (69.3) −9.7 (−11.2, −8.3) 4155 (86.3) 3812 (79.2) −7.1 (−8.3, −5.9)
Benzodiazepine 1946 (45.8) 1834 (43.2) −2.6 (−4.0, −1.3) 2847 (59.1) 2625 (54.5) −4.5 (−5.9, −3.3)
Buprenorphine for MAT 291 (6.9) 348 (8.2) 1.3 (0.5, 2.0) 204 (4.2) 245 (5.1) 0.9 (0.2, 1.5)
Stimulant 221 (5.2) 186 (4.4) −0.8 (−1.3, −0.3) 183 (3.8) 163 (3.4) −0.4 (−0.8, 0)
Muscle relaxant 341 (8.0) 234 (5.5) −2.5 (−3.2, −1.9) 431 (8.9) 281 (5.8) −3.1 (−3.8, −2.5)
Concurrent opioid and benzodiazepine 1620 (38.2) 1449 (34.1) −4.1 (−5.3, −2.8) 2546 (52.9) 2208 (45.9) −7.0 (−8.3, −5.8)

90 days before and after first non-fatal overdose

Any prescription 3073 (72.4) 2751 (64.8) −7.6 (−8.9, −6.2) 3923 (81.5) 3696 (76.7) −4.8 (−5.8, −3.6)
Opioid for pain 2674 (63.0) 2266 (53.4) −9.6 (−11.0, 8.2) 3617 (75.1) 3255 (67.6) −7.5 (−8.8, −6.3)
Benzodiazepine 1581 (37.2) 1460 (34.4) −2.8 (−3.9, −1.8) 2385 (49.5) 2182 (45.3) −4.2 (−5.4, −3.1)
Buprenorphine for MAT 163 (3.8) 176 (4.1) 0.3 (−0.3, 0.9) 100 (2.1) 132 (2.7) 0.6 (0.2, 1.1)
Stimulant 161 (3.8) 138 (3.3) −0.5 (−0.9, −0.2) 139 (2.9) 117 (2.4) −0.5 (−0.8, −0.1)
Muscle relaxant 230 (5.4) 181 (4.3) −1.1 (−1.6, −0.7) 282 (5.9) 218 (4.5) −1.4 (−1.8, −0.9)
Concurrent opioid and benzodiazepine 1276 (30.1) 1092 (25.7) −4.4 (−5.3, −3.3) 2111 (43.8) 1784 (37.0) −6.8 (−7.9, −5.6)

MAT = medication assisted treatment; TN = Tennessee; HDDS=Hospital Discharge Data System; CSMD = Controlled Substance Monitoring Database.
a
= % difference.

frequently filled prescriptions in the year before both opioid and heroin
overdoses, respectively. A similar dispensing pattern of drug types was
observed in the year before overdose among inpatients.
In the year after an opioid overdose, hydrocodone SA, oxycodone
SA, alprazolam, and tramadol SA were the most commonly filled pre-
scriptions after both ED and IP discharges.
Compared to those discharged from the ED, slightly higher pro-
portions of patients after an IP stay for a heroin overdose had filled
alprazolam (9.9% vs. 7.6%), tramadol SA (8.6% vs. 7.9%), oxycodone
SA (19.7% vs. 16.6%) and hydrocodone SA (29.6% vs. 24.2%). The
other commonly filled prescription after a heroin overdose was clona-
zepam (6.8% after both ED and IP overdose discharges). Details on the
distribution of other drug types dispensed in the year before and after
an overdose are given in Web Appendix C. We conducted a similar
analysis for drug types filled within 90 days of overdoses shown in Web
Appendix D. In our study, Medicaid was used less to fill a prescription
by any overdose type. Cash and commercial insurance were used more
frequently to fill up prescriptions by both opioid and heroin overdose
patients (Web Appendix E).
4. Discussion
Prescriptions for controlled substances decreased after discharge for
overdose regardless of treatment setting or type of drug dispensed.
However, the proportion of patients filling buprenorphine for MAT did
not show an appreciable increase after all drug and opioid overdoses.
Compared to ED patients, higher proportions of patients treated in in-
patient units for any type of drug overdose filled opioid analgesics and
benzodiazepines after an overdose, while buprenorphine for MAT was
filled less among patients who were treated in an inpatient unit com-
pared to those treated in the ED. This may reflect unknowable in-
formation about the patients and the specific overdose; namely whether
it was more or less likely to be in the context of a substance use dis-
order. It is important to note that many prescription drug overdoses

Table 4
Change in opioid, benzodiazepine, and stimulant prescribing before and after the first non-fatal, heroin overdose (TN HDDS: 2013–2016, CSMD: 2012–2017).
Emergency department visits (n = 1666) Inpatient stays (385)

Before n (%) After n (%) Differencea (95% CI) Before n (%) After n (%) Differencea (95% CI)

365 days before and after first non-fatal overdose

Any prescription 1122 (67.3) 931 (55.9) −11.4 (−14.4, −8.6) 256 (66.5) 222 (57.7) - 8.8 (−14.7, −3.0)
Opioid for pain 848 (50.9) 644 (38.7) −12.2 (−15.2, −9.3) 196 (50.9) 162 (42.1) - 8.8 (−15.0, − 2.7)
Benzodiazepine 360 (21.6) 283 (17.0) −4.6 (−6.5, −2.7) 96 (24.9) 82 (21.3) −3.6 (−8.1, 0.8)
Buprenorphine for MAT 271 (16.3) 267 (16.0) −0.3 (−2.4, 1.9) 63 (16.4) 47 (12.2) −4.2 (−7.9, −0.4)
Stimulant 127 (7.6) 89 (5.3) −2.3 (−3.3, −1.2) 27 (7.0) 25 (6.5) −0.5 (−2.9, 1.9)
Muscle relaxant 36 (2.2) 23 (1.4) −0.8 (−1.4, −0.2) 8 (2.1) 6 (1.6) −0.5 (−1.8, 0.7)
Concurrent opioid and benzodiazepine 169 (10.1) 115 (6.9) −3.2 (−4.6, −1.9) 52 (13.5) 51 (13.3) −0.2 (−3.6, 3.1)

90 days before and after first non-fatal overdose

Any prescription 619 (37.2) 553 (33.2) −4.0 (−6.4, −1.5) 157 (40.8) 147 (38.2) −2.6 (−8.0, 2.8)
Opioid for pain 407 (24.4) 312 (18.7) −5.7 (−7.9, −3.5) 98 (25.5) 98 (25.5) 0 (−5.1, 5.1)
Benzodiazepine 206 (12.4) 190 (11.4) −1.0 (−2.2, 0.3) 58 (15.1) 54 (14.0) −1.1 (−4.3, 2.3)
Buprenorphine for MAT 101 (6.1) 136 (8.2) 2.1 (0.7, 3.5) 31 (8.1) 28 (7.3) −0.8 (−3.8, 2.2)
Stimulant 78 (4.7) 64 (3.8) −0.9 (−1.5, −0.1) 20 (5.2) 21 (5.5) 0.3 (−1.7, 2.2)
Muscle relaxant 16 (1.0) 17 (1.0) 0 (−0.4, 0.5) 3 (0.8) 4 (1.0) 0.2 (−0.2, 0.8)
Concurrent opioid and benzodiazepine 87 (5.2) 66 (4.0) −1.2 (−2.1, −0.4) 26 (6.8) 32 (8.3) 1.5 (−1.1, 4.2)

MAT = medication assisted treatment; TN = Tennessee; HDDS=Hospital Discharge Data System; CSMD = Controlled Substance Monitoring Database.
a
= % difference.

5
S. Krishnaswami, et al.
Fig. 1. Filled prescription drug types in the year before and after all drug, opioid, heroin non-fatal overdose Emergency Department visits (TN, HDDS: 2013–2016,
CSMD: 2012–2017).
may reflect accidental misuse of drugs and not an ongoing problem.
After a heroin overdose, prescriptions overall decreased. Among the
specific drug types, hydrocodone SA, oxycodone SA, alprazolam and
tramadol SA were the most commonly filled prescriptions in the year
after both IP and ED opioid and heroin overdoses.
The dispensing patterns of CS observed in our study are consistent
with the literature and reflect ongoing high levels of prescribing, even
in the presence of an overdose event. Generally, our study had similar
results to other studies on the subject, both in terms of the patient
population and outcomes, even though other studies typically did not
have the benefit of a complete PDMP data set and often relied on
claims. That said, other than one Medicaid focused study (Fulton-Kehoe
et al., 2015), our analysis suggested that Tennesseans had higher levels
of pre-overdose opioid prescribing (Frazier et al., 2017; Olfson et al.,
2018; Smolina et al., 2019; Geissert et al., 2018; Boscarino et al., 2016).
Data on post-overdose prescribing varies in the literature; among
four similar studies, ours showed a similar proportion of patients re-
prescribed (70%) (Boscarino et al., 2016) with others either sub-
stantially higher (91%) (Larochelle et al., 2016), or lower (39.7%)
(Frazier et al., 2017). In general, opioid prescriptions do decrease after
policies are implemented to affect prescribing (Osborn et al., 2017)
which could reduce non-fatal opioid overdoses, but increase heroin
overdoses (Brown et al., 2017). In a study conducted among Medicaid
enrollees in Pennsylvania (Frazier et al., 2017) using outpatient and IP
claims data, opioid analgesics decreased by 6.5% and 3.5% six months
after opioid and heroin overdoses, respectively, compared to a higher
decrease observed in the year after opioid and heroin overdoses in our
study. Our results on concurrent opioid –benzodiazepine prescriptions
6
Preventive Medicine 130 (2020) 105883
after an ED opioid overdose was similar to the results previously ob-
served (Larochelle et al., 2016).
In general, our results also suggest that MAT was underutilized in
TN during the years of our study, with only minimal increases seen in
MAT use in the year after overdose. It is troubling that patients gen-
erally continue to receive prescription opioid analgesics after an over-
dose, with limited uptake of buprenorphine for MAT, which is the
primary medical approach available in Tennessee for treating substance
use disorder. In TN, buprenorphine is frequently filled as a combination
product with naloxone which is an opioid reversal drug (Albert et al.,
2011; Darke et al., 2007; Morizio et al., 2017; Cash et al., 2018). Me-
thadone is only available at a relatively small number of locations
(n = 13) that are under the purview of the State Department of Mental
Health and Substance Abuse Services.
Tennessee does not have a statewide health information exchange
and it is likely that clinicians re-prescribing to patients who experienced
an overdose may be completely unaware that the overdose occurred. In
TN, there is no established system to routinely notify primary care
providers after an ED or inpatient visit for an overdose. We do not know
at this time if patients continue to receive prescriptions from the same
provider after overdose. The differences between our study and others
are possibly because of the difference in the timing of assessment before
overdose, or type of discharge setting or study time-frame or char-
acteristics of subjects included.
4.1. Strengths and limitations
To our knowledge, this is the first study in TN to evaluate change in
S. Krishnaswami, et al.
Fig. 2. Filled prescription drug types in the year before and after all drug, opioid, heroin non-fatal overdose Inpatient stays (TN, HDDS: 2013–2016, CSMD:
2012–2017).
dispensing of CS around all drug, opioid, and heroin non-fatal over-
doses using PDMP data, which covers statewide use of CS in outpatient
and IP settings and provide details on payment method for prescriptions
including those paid by cash. Study strengths include a large sample
size of linked hospital billing data with detailed prescription dispensing
information including drug class and specific types of prescription
drugs in the year before and after ED or IP overdose. We examined
results for inpatient overdoses and ED overdoses separately, which
provided more targeted data on prescribing practices in this population.
However, several limitations should be considered. First, results are
limited to discharges from TN acute care hospitals for the first non-fatal
drug overdose during the study time-frame, and may not be general-
izable to populations who have repeat overdoses or other states with
different demographic profiles. Misclassification of overdoses could
have occurred due to diagnostic coding errors, however we used defi-
nitions established by experts with extensive experience using hospital
billing data for drug overdose surveillance (CDC's Opioid Overdose
Indicator Support Toolkit, 2018). Another limitation is that overdoses
that occurred in the community or overdoses to TN residents at hos-
pitals out of state were not included, resulting in an underestimation of
non-fatal overdoses. TN's CSMD does not include information on the
indication for prescription and we are limited to using the FDA-label
indication. It is also not known if the patients actually took the medi-
cations as only dispensed data are available. Unfortunately, we are also
not aware about how many of our residents fill a prescription out of
state. Due to limited identifiers, our linking process may have missed
both non-fatal overdoses and prescription records. Even though there is
a general trend of decreasing opioid analgesic prescriptions over time,
the change estimates observed in our study are unlikely to be solely due
7
Preventive Medicine 130 (2020) 105883
to policy changes or secular trends as much of our study period predates
the release of guideline for prescription opioids for chronic pain
(Dowell et al., 2016) and the number of patients filling opioid analge-
sics started to show a steady decline only from 2015 Q3 in TN
(Tennessee Department of Health, Office of Informatics and Analytics,
2019).
5. Conclusions
This study provides a comprehensive description of prescribing
patterns in the year before and after a non-fatal overdose in Tennessee.
The overall conclusion is that prescribing is common in Tennessee be-
fore an overdose, does not decrease appreciably afterward, and MAT
may be underutilized as increases in buprenorphine were not observed
after overdose events. This should provide a framework for education
for clinicians and the public, and highlights the challenge of a health
data system in which prescribing clinicians can be unaware that their
patients experienced an overdose event. The lack of buprenorphine
increase may also point to the importance of initiating MAT while the
patient is in the ED with a referral to primary care, treatment centers
and supporting programs that offer provider education and patient
counseling for better coordinated care to prevent fatal and non-fatal
outcomes. Additional studies on polydrug non-fatal overdoses are
warranted.
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.ypmed.2019.105883.
S. Krishnaswami, et al.
Funding
This work was supported by the Centers for Disease Control and
Prevention, Prescription Drug Overdose Prevention for States Program
(5 NU17CE002731-02-00)] to the Tennessee Department of Health. The
funding agency had no role in study design, analysis or preparation of
the manuscript.
Acknowledgments
Dr. Krishnaswami and Dr. Nechuta designed the study and acquired
the data for the study. Dr. Krishnaswami conducted the primary ana-
lyses and wrote the first draft of the manuscript. All authors contributed
to the data creation, analysis and/or interpretation. All authors have
contributed to and approved the final manuscript for publication.
Authors thank Nancy Liu for her assistance with bibliography and
formatting of the tables and Molly Golladay for help with cleaning of
names collected in the prescription database and Dr. Ben Tyndall for
help with cleaning of names collected in the hospital database.
Declaration of competing interest
The authors have no conflict of interest to declare. The findings and
conclusions in this report are those of the authors and do not necessarily
represent the official position of the Centers for Disease Control &
Prevention or Tennessee Department of Health.
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