Opioid Dependence Treatment Therapies in Pregnancy

Objective:

The goal of this proposal is to conduct a pilot study to establish the feasibility and
acceptability of a randomized comparative effectiveness clinical trial comparing office-based
buprenorphine vs. federally licensed methadone programs for the treatment of opioid dependent
pregnant women.

Specific Aims:

Aim 1: Evaluate the feasibility of conducting a randomized study comparing office-based
buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant
women. OD pregnant women (n=50) will be randomized (1:1) to office-based buprenorphine vs. a
federally licensed methadone program. Feasibility will be assessed by measuring the
proportion of OD pregnant women who are eligible, who enroll, who remain in the study and by
the ability to monitor treatment program factors (e.g. compliance with treatment
provider/facility visits, counseling sessions, prenatal care visits, social services
involvement) and maternal treatment outcomes such as treatment retention, illicit drug use
and HIV risk behavior.

Aim 2: Describe the perspectives of OD pregnant women and their providers regarding
buprenorphine vs. methadone for the treatment of opioid dependence in pregnancy. Study
acceptability will be assessed by conducting qualitative semi-structured interviews with
three groups: (1) pilot participants to determine their satisfaction with the assigned
treatment program and identify mismatches between treatment program services and
participants' needs; (2) prenatal care and opioid treatment providers to identify ways to
improve the treatment process in pregnancy and to suggest ideas for care coordination; (3) OD
pregnant women who are ineligible or who choose not to participate in the pilot trial will
also be asked to participate in an interview to gain a broader perspective of attitudes and
perspectives regarding opioid treatment programs in pregnancy.

Aim 3: Identify barriers and facilitators to treatment retention in the postpartum period and
identify key functional outcomes relevant to reductions in illicit drug use during pregnancy.
Illicit drug use relapse is most common in the immediate postpartum period when stresses
associated with motherhood are the greatest. Therefore, pilot participants will be followed
at 3, 6, 9 and 12 weeks postpartum to identify barriers and facilitators specific to the
postpartum period that may impact treatment retention. The relationship between postpartum
treatment retention and maternal functional outcomes will also be explored (e.g.
breastfeeding, postpartum depression, motherhood satisfaction, infant custody, employment,
and criminality).

Background:

The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to
5.8 per 1,000 hospital births per year. While methadone is the current, standard treatment
for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative.
In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal
outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS)
compared to methadone. However, buprenorphine was also associated with greater study
discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone.
Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing
any short-term improvement in neonatal outcomes. Therefore, the next research question that
emerges is which is the most effective treatment (buprenorphine vs. methadone) for a
particular patient during pregnancy?

In clinical settings, differences in maternal characteristics, treatment program structure
and patient and provider preferences may surpass the impact of pharmacology on maternal
treatment outcomes (treatment retention, illicit drug use, HIV risk behavior). Buprenorphine
is dispensed in office-based settings by a variety of providers and with less regulatory
oversight than methadone. Methadone is dispensed from federally licensed facilities that
often incorporate counseling and support services into treatment protocols. Successful
office-based treatment relies on shared power and responsibility, close patient-provider
relationships and careful attention to psychosocial co-morbidities. Failure to match patient
problem severity to differences in treatment program structure may contribute to adverse
maternal outcomes. Therefore, to understand the comparative effectiveness of buprenorphine
vs. methadone in pregnancy, the impact of patient problem severity and treatment program
structure on maternal (vs. neonatal) outcomes must be compared.

Significance:

Findings from this project will provide the preliminary data to support a comparative
effectiveness clinical trial designed to compare the impact of office-based buprenorphine vs.
federally licensed methadone programs on maternal treatment and postpartum functional
outcomes in OD women. The ultimate goal of this line of research is develop evidence-based
clinical guidelines to guide provider decision-making regarding the most effective treatment
(buprenorphine vs. methadone) for a particular patient during pregnancy.

Inclusion Criteria:

- Pregnant women 18+ years old, with a singleton pregnancy ≤ 28 weeks gestation
confirmed by ultrasound, who meet Diagnostic and Statistical Manual-IV criteria for
opioid dependence confirmed by urine drug screen (UDS), who are interested in opioid
maintenance treatment and plan to receive prenatal care and deliver at Magee Womens
Hospital (MWH) will be recruited.

Exclusion Criteria:

- (1) active, current dependence on benzodiazepines or alcohol

- (2) acute severe psychiatric condition in need of immediate treatment (e.g. suicidal
ideations)

- (3) pending or legal action that could prohibit or interfere with participation (e.g.
incarceration)

- (4) current, established treatment with methadone or buprenorphine. Exclusion criteria
are based on the Substance Abuse and Mental Health Services Administration (SAMHSA)
recommendations for office-based buprenorphine use.