Assignment D

http://taylorandfrancis.com/iada 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

P E R S P E C T I V E

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 pharma- cological 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 heroin-

exposed 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

2009. 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 legisla-

tion 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 prescrip-

tion 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 opioid-

addicted women reflect simply an ill-advised political deci-

sion 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 evidence-

based 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 mainten-

ance 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 predic-

tions (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 non-

injection 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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