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ISSN: 0095-2990 (print), 1097-9891 (electronic)
Am J Drug Alcohol Abuse, 2015; 41(5): 367–370
! 2015 Taylor & Francis Group, LLC. DOI: 10.3109/00952990.2015.1047502
PERSPECTIVE
Opioid use disorder during pregnancy in Tennessee: expediency vs.
science
Peter R. Martin, MD and A. J. Reid Finlayson, MD
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
Abstract
Methadone and buprenorphine are highly effective and commonly prescribed for the
treatment of opioid use disorder. Both medications are also efficacious for the treatment of
pregnant women with this disorder. In one third of states, however, Medicaid reimbursement
will cover the cost of buprenorphine, but not methadone, to treat opioid use disorder in
pregnant women. This commentary will explore the clinical and policy rational and
consequences of this policy, with the opinion that this approach is guided by political
expediency rather than sound clinical research. The commentary will focus on the pharmacological management of prescription opioid dependence during pregnancy in Tennessee, one
of the states that restrict Medicaid coverage of pregnant women to buprenorphine. Tennessee
is also relevant in that this state ranks second nationally in the rate of prescriptions written for
opioid pain relievers; in contrast to injection opioid use in urban populations, opioid addiction
in rural and southeastern regions of the US is characterized by use of non-injection prescription
opioids. Until recently, most research-based recommendations for the management of opioid
use disorder during pregnancy have derived from studies of women using opioids
intravenously. The lack of research in non-injection opioid-using pregnant women may
partially explain why policy rather than scientific evidence guides Medicaid reimbursement. It is
hoped that future research in pregnant women addicted to prescription opioids will clarify
which opioid addicted pregnant women have better outcomes with buprenorphine or
methadone treatment and these findings, in turn, will inform Medicaid reimbursement.
Keywords
Buprenorphine, methadone, opioid use
disorder, pregnancy, policy
History
Received 12 January 2015
Revised 20 April 2015
Accepted 21 April 2015
Published online 15 July 2015
A growing public health concern
Opioid use disorder in pregnancy is of mounting public health
concern in our country, complicating an estimated 54 000
pregnancies annually (1). A wide range of consequences of
opioid exposure during pregnancy for mother, fetus, and the
neonate have been described and questions persist as to
whether adverse effects continue into infant development and
beyond (2). Neonatal abstinence syndrome (NAS) is a
postnatal withdrawal syndrome, first described in heroinexposed newborns; more recently, other factors than opioid
exposure have also been implicated in this clinical syndrome
(3). NAS presents with an array of clinical signs, including
feeding difficulty, autonomic dysfunction, and behavioral
distress. NAS has become widely recognized as a major
healthcare expenditure associated with opioid use disorder
during pregnancy and accordingly has been identified as an
important focus for prevention efforts (4). The incidence of
NAS increased substantially in the United States between
2000 and 2009 (3). This increase has been striking in
Tennessee, where 29% of pregnant women enrolled in
Medicaid (TennCare) filled opioid prescriptions during
- From 1995–2009, pregnancy-related use of opioid
analgesics nearly doubled among TennCare participants (5).
From 2009–2011, the rate of NAS among infants in TennCare
increased from 6.0–10.7 per 1000 births (6) and to 11.6 in
2013 (4) – representing a 16-fold increase since 2000. This
commentary focuses on opioid agonist treatment as a
significant component of the management of prescription
opioid use disorder during pregnancy in Tennessee, of
particular interest, as this state ranked second nationally in
the rate of prescriptions written for opioid pain relievers, at
1.4 per person in 2012 (7). In rural and southeastern regions
of the United States, such as Tennessee, where opioid
addiction is predominantly characterized by non-injection
use of prescription opioids, available therapeutic choices for
opioid use disorder have become limited to buprenorphine
instead of methadone, seemingly a policy decision, not one
guided by the available scientific evidence which supports the
efficacy of both medications.
Address correspondence to Peter R. Martin, Department of Psychiatry,
Vanderbilt University, School of Medicine, 1601 23rd Avenue South,
Suite 3068, Nashville, TN 37212, USA. E-mail: peter.martin@
vanderbilt.edu
The Tennessee approach: criminalization to
‘‘encourage’’ treatment but no Medicaid access
to methadone
Even these very high rates of NAS in Tennessee likely
underestimate the use of opioids during pregnancy because of
significant underreporting due to stigma associated with drug
use disorders. This stigma is greatly exacerbated by recent
Tennessee legislation which ‘‘allows prosecution of a woman
for assault for the illegal use of a narcotic drug while
pregnant, if her child is born addicted to or harmed by the
narcotic drug and the addiction or harm is a result of
her illegal use of a narcotic drug taken while pregnant’’
(http://state.tn.us/sos/acts/108/pub/pc0820.pdf). This legislation clearly may deter pregnant women from seeking prenatal
care for fear of being reported. However, the law should also
be viewed as offering incentive for addiction treatment and
recovery as it next states that, ‘‘It is an affirmative defense to
a prosecution … that the woman actively enrolled in an
addiction recovery program before the child is born, remained
in the program after delivery, and successfully completed the
program, regardless of whether the child was born addicted to
or harmed by the narcotic drug.’’ Interpretation of this
legislation is challenging based on recent findings that opioid
type, including methadone and buprenorphine maintenance,
and tobacco and SSRI antidepressant use all significantly
increase risk of NAS (6).
In order to attempt to contain the prescription opioid
epidemic in the state, the Tennessee Department of Health has
implemented a Controlled Substance Monitoring Database
(CSMD) program and mandatory education for prescribers
(http://health.state.tn.us/boards/ControlledSubstance/index.
shtml). This program mandates that pharmacies record all
controlled drug prescriptions in a centralized database that
physicians must search in real-time prior to providing a
prescription for a controlled drug to any patient. However, the
high incidence of NAS has not diminished, so much so that
the first statewide surveillance system for NAS was recently
implemented by the Tennessee Department of Health to allow
study of prevention of this serious complication of prescription opioid dependence (4).
Options for management of opioid use disorder during
pregnancy include maintenance on an opioid agonist approved
for addiction treatment or detoxification (1). With careful
monitoring, the prescribed opioid analgesic may also be
continued or discontinued slowly by tapering. Detoxification
from opioids during pregnancy has not been the recommended
course for more than 40 years, particularly not for women with
the most severe form of opioid use disorder, namely those who
use intravenous opioids; such pregnant women are very unlikely
to be able to avoid relapse without pharmacological support (8).
Methadone maintenance treatment, as currently widely
employed throughout the United States, remains the standard
of care for agonist treatment of opioid use disorder in pregnancy
(1). Although consensus holds methadone maintenance as the
standard against which other treatments of pregnant women
with opioid use disorder must be compared, TennCare does not
cover the cost of methadone maintenance. Tennessee is not
alone: approximately a third of states do not provide for
methadone maintenance treatment of pregnant women (9).
Policy rather than evidence-guided clinical practice?
Disparities among states in Medicaid support for treatment of
these pregnant women is not easily understood by examining
the published evidence alone. Does excluding methadone
from the therapeutic armamentarium for pregnant opioidaddicted women reflect simply an ill-advised political decision or are these appropriate regional policies because
relevant evidence supporting methadone maintenance in
their populations is not readily available? State laws and
regulations pose significant implications for practitioners in
that policy might influence clinical practice in a manner that
is not entirely consistent with recommendations in the
scientific literature (10).
Without opioid agonist treatment, which reduces drug
craving and use, those who are addicted to intravenous
opioids are recognized to be at a particularly high risk of
relapse and consequently opioid overdose, premature labor
triggered by repeated episodes of withdrawal, exposure to
intravenously transmitted infections, and consequences of
involvement with the criminal justice system. Evidence-based
treatment includes administration of a therapeutic daily dose
of methadone provided within the context of a comprehensive
treatment program comprising psychiatric and obstetrical
prenatal care, counseling and group therapy, and social work
services (11). Methadone maintenance in comparison with
active intravenous opioid addiction has been shown to result
in improved adherence to prenatal care, increased fetal
growth, and decreased risk of HIV infection, preeclampsia,
and foster care placement of the neonate. Nevertheless, NAS
of significant severity to require treatment with morphine is
still observed in well over 50% of pregnancies on methadone
maintenance (12). Hence, if absence of NAS is one criterion
for treatment efficacy, as inferred from the above-mentioned
Tennessee law, methadone maintenance, while it is evidencebased practice, may not be the best we can do. Also, focusing
solely on NAS, as the Tennessee law does, misses the
possibility that women who relapse during pregnancy may
never even reach delivery because of complications of
accelerated opioid use disorder (13,14).
Changing face of opioid addiction
By not covering methadone costs, TennCare, like Medicaid in
the other non-methadone states, limits access to methadone,
but it does ensure that opioid-dependent Tennesseans can
receive buprenorphine during pregnancy at a limited daily
dose, with prior authorization (http://www.tn.gov/tenncare/
forms/ben11001.pdf). This policy may be a reflection of the
changing face of opioid addiction among pregnant women
due to an ever-expanding prescription opioid epidemic (1).
From a problem affecting predominantly disenfranchised
inner city women using intravenous heroin, a much larger,
demographically diverse population addicted to prescription
opioid analgesics has become widely distributed throughout
smaller urban and rural regions of the United States. This
increase in prescription opioid use disorder is characteristic of
southeastern states, including Tennessee. Not only is the
pattern of opioid use different in the Southeast and in rural
regions, but this pattern of opioid addiction represents a
considerably larger challenge in absolute numbers than do
368 P. R. Martin & A. J. Reid Finlayson Am J Drug Alcohol Abuse, 2015; 41(5): 367–370
injection opioid users. For example, in 1997, annual quantities
of opioid pain relievers prescribed were equivalent to 96 mg
of morphine per individual; by 2007, rates had reached the
equivalent of 700 mg of morphine per person. In 2010,
2 004 000 persons aged 12 or older initiated non-medical
opioid pain reliever use (almost as high as the 2 426 000 for
marijuana) compared to only 140 000 for heroin (15). These
trends suggest that management of non-injection prescription
opioid use during pregnancy will continue as a major clinical
challenge and that states like Tennessee may be legislating
care based upon epidemiologic data. However, methadone
treatment in pregnancy standards were established in large
urban areas from which most of the NIH-funded research
guiding practitioners, to date, has been conducted.
Management of non-injection vs. injection
opioid addiction
Although non-injection opioid addiction has fewer severe
medical complications than injection drug use (16), overdose
deaths due to opioid analgesics recently surpassed heroin and
cocaine, rivaling death rates from motor vehicle accidents in
absolute terms as reported by the CDC (17). So, while
ingested prescription opioids have been considered a ‘‘safer’’
dosage form compared to intravenously administered opioids,
consequences of these drugs are far from benign and cannot
be ignored. In fact, an increasingly common clinical trajectory
is to switch to intravenous or smoked heroin from prescription
opioids (13,14) based upon changing supply and demand,
unintended consequences of tighter regulation of prescribing.
Despite the fact that we do not really know which patients
(injection or non-injection) do better on methadone or on
buprenorphine, TennCare and the Medicaid formularies of
many demographically similar states provide buprenorphine
rather than methadone for opioid use disorder treatment.
While it would be ideal to determine for each individual
whether a partial (buprenorphine) or full (methadone) mu
opioid agonist combined with structured psychosocial care of
the mother during gestation can result in a healthier neonate at
the point when opioid exposure stops at delivery (1), the other
extreme, a public health approach, attempts to reach
the greatest number of patients with an evidence-based
approach (18).
The risk-benefit analysis supporting methadone maintenance for intravenous opioid addicted pregnant women is very
compelling (8,19,20), but comparable studies in non-injection
opioid use disorder patients, who obtain these drugs from the
street or by prescription from their doctors for pain control,
are only now emerging from other rural states like Vermont.
The findings suggest that buprenorphine is equal to, or may
be even better, for prescription opioid addicted pregnant
women (21). The situation is somewhat more complicated by
the fact that the route of heroin administration has change
dramatically in the past 10 years due to the purity of the drug
that allows for smoking or snorting (22). It may be argued that
some of these women addicted to prescription opioids may
well be detoxified or tapered off the opioid, thus avoiding
NAS for their child. However, the likelihood of continued
abstinence without maintenance treatment is not very high in
oral prescription opioid use disorder either (23); hence, the
risks of repeated cycles of intoxication and withdrawal, albeit
less severe, do exist with prescription opioids as well. A case
can thus be made for maintenance with an opioid agonist to
reduce craving and risky use, but these women may not
require the intensive (expensive and time-consuming) daily
monitoring mandated by law for methadone maintenance.
Buprenorphine maintenance: the practical choice
for pregnant prescription opioid addicts
Buprenorphine appears to be a particularly appropriate choice
for management of the pregnant prescription opioid addict
because it has been approved for office-based maintenance of
opioid addiction, thus eliminating barriers associated with
daily visits to a methadone clinic. Buprenorphine can be used
during pregnancy with little risk to the fetus, and pregnancy
outcomes are not significantly different from those obtained
with methadone (24). Buprenorphine, a partial mu opioid
agonist and kappa opioid antagonist, causes less activation of,
and has greater affinity for the mu-opioid receptor than
methadone. Additionally, there is less placental transfer of
buprenorphine than methadone. These considerations, in
theory, should lead to decreased physical dependence of the
fetus with buprenorphine and less severe associated NAS
upon delivery. The MOTHER study, a randomized controlled
trial comparing buprenorphine and methadone exposure
during pregnancy, provided some support for these predictions (12). Infants exposed to buprenorphine during gestation
were found to spend fewer days in the hospital and required
lower morphine doses over a shorter treatment period for
NAS than those exposed to methadone, while both opioid
agonists were equally well tolerated and effective in
decreasing illicit drug use.
Further research is needed to determine the appropriate
clinical threshold for opioid prescribing in pregnancy,
including opioid agonist maintenance in women who are
addicted to prescription opioids and use them only via noninjection routes. This is possibly a different population than
that from which most of the existing research guiding
treatment is currently available.
Declaration of interest
The authors report no conflicts of interest. The authors alone
are responsible for the content and writing of this paper.
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