Can New Medication Formulations for Opioid Addiction Prevent Relapse in New Parents?

Over the last decade, opioid use has quadrupled in pregnant persons, with overdose becoming a leading cause of pregnancy-related death. As the opioid crisis impacts this demographic, there is urgency within the medical community to expand expertise and treatment options to improve care.

Maternal relapse rates peak in the first year after birth, when new parents face gaps in care while also juggling the constraints and demands of a newborn. Difficulty managing a daily medication regimen for the treatment of opioid use disorder (OUD) may also be a factor in returning to non-prescribed use, believe Boston Medical Center’s Kelley Saia, MD, and Elisha Wachman, MD.

Methadone — one medication for OUD — is highly regulated and only dispensed at specific opioid treatment centers, requiring frequent travel to obtain the medication. Another treatment, sublingual buprenorphine, is often taken several times a day. Longer-acting injectables do exist for OUD, like once-monthly buprenorphine extended-release (BXR) and naltrexone extended-release, but safety in pregnancy, the post-partum period, and during lactation remains understudied. 

HealthCity recently spoke with Saia, director of BMC’s high-risk obstetrical and addiction recovery program Project RESPECT, and Wachman, a BMC neonatologist and leading NOWS researcher, regarding the care barriers facing pregnant and new mothers with OUD, the urgency to streamline care for these patients, and two new studies underway at BMC to investigate longer-acting treatment options.

HealthCity: Can you describe the obstacles facing pregnant people and new parents with opioid use disorder? What does treatment look like for this demographic?

Kelley Saia, MD: Generally, when a person with SUD becomes pregnant, fetal health becomes the priority, and maternal health comes second. Patients are encouraged to either stop the addiction treatment they’re on or change it because the safety in pregnancy and/or breastfeeding is not well studied.

Methadone is highly effective treatment — but patients must present to their methadone clinic every day for their dose. It requires time and money for daily transportation, which is a barrier for everyone, but particularly for parents with newborns. Sublingual buprenorphine is prescribed and designed for a nonpregnant person to take once a day, but in pregnancy, the treatment works better by taking multiple doses throughout the day. Many pregnant patients cannot tolerate sublingual buprenorphine because of morning sickness. Without their buprenorphine, their nausea worsens as withdrawal symptoms begin. It becomes a horrible cycle. If we could give injectable buprenorphine, BXR, we could prevent this cycle and provide improved treatment options for many people.

Elisha Wachman, MD: The first year after delivery, particularly 6 to 12 months postpartum, is a really high-risk time for return to non-prescribed use because of all the stressors in new parents’ lives. They have a new infant, and there are often new challenges — for example, they may be discharged from a residential program after they’re stable. All of the supports — like frequent recovery support and prenatal care appointments, residential treatment, intensive social work and early intervention services — that they had during pregnancy to promote the health of the baby start disappearing.

HC: How could longer-lasting medications for opioid use disorder help pregnant people and breastfeeding parents? Are there downsides?

EW: The idea of having a longer-acting medication like buprenorphine extended-release could potentially help stabilize people, particularly in the higher-risk period after birth. It’s a once-a-month commitment versus remembering to pick up your prescription and take it multiple times a day or check in with the clinic.

The problem with BXR is that it has never been studied in pregnancy or in the postpartum period. The reason that it hasn’t been studied is that the injection contains not only the medication but other additives to stabilize it. One particular component within the formulation, called NMP, was shown to be potentially teratogenic, meaning that it can disturb the development of a fetus or embryo. However, the only information we have is based off high-dose administration in some animal studies in the 1970s — a very long time ago. Although it’s different from the small amount that’s added to the injection, it makes providers very hesitant to recommend its use it in pregnancy or postpartum, not knowing if it is transferred through breastmilk.

KS: Six years ago, we had about five or six patients with opioid use disorder who had been stable on Vivitrol, naltrexone extended-release, when they became pregnant. Their Vivitrol providers were not comfortable administering Vivitrol to pregnant persons and stopped prescribing. By the time they presented to us, they had returned to opioid use.

You can imagine that if we had data to support those providers and say, “no, it’s safe to continue these folks on Vivitrol,” how different their outcomes would be. That is why we are undertaking new studies on extended-release naltrexone and buprenorphine at Boston Medical Center. Additionally, injectable buprenorphine needs to be an option for pregnant people. And we’ve had several patients who would’ve had much better outcomes had injectable buprenorphine been available in a formulation that was safe in pregnancy.

HC: What studies are currently underway at Boston Medical Center to investigate longer-acting medications for opioid use disorder during pregnancy and postpartum?

KS: BMC is one of two sites in a National Institutes of Health-funded study investigating extended-release naltrexone (Vivitrol) for pregnant people with opioid use disorder, though we’ve recently expanded the study to include alcohol use disorder and are now enrolling participants with either disorder. Alcohol use in pregnancy is the most common, preventable cause of birth defects, and there are only few treatment options in pregnancy.

EW: We are also enrolling for a small study on buprenorphine extended-release in postpartum breastfeeding individuals — aiming for just 10 patients. We think the first step is to study it in people who had been stabilized on buprenorphine sublingually through their pregnancy and are now postpartum and still providing breast milk. We will examine the levels of exposure to the baby through whatever amount is being transferred through the breast milk. We hypothesize that it’s an incredibly low amount that would not cause any harm. So, measuring it is to determine if the levels are more stable over the course of the month versus the ups and downs that happen with the daily administration of sublingual medication.

We will also measure the levels of the NMP additive in mom, baby, and breast milk. The overall assumption is that the risk of exposure to this additive is likely pretty low. If we show that it is safe in this population, we can study this in pregnancy and look at longer-term outcomes.

Ultimately, we would like to compare the health outcomes at least a year postpartum and look at the range of retention and treatment in parents using injectable buprenorphine versus other medications for OUD.

Again, evidence we have from nonpregnant patients shows that buprenorphine extended-release is a highly effective treatment. These studies will hopefully make it a treatment option that other institutions feel more comfortable offering to pregnant and postpartum patients.

HealthCity: Expanding medication options is just one piece of improving care for pregnant and postpartum people with opioid addiction. What are other ways you want to see care improve for this population?

KS: BMC provides a spectrum of addiction treatment services which is rare and we have over 30 years of experience caring for pregnant people with SUDs. We continue to improve and expand the services we provide. We are innovating our wraparound services, like our medical-legal representation, which has the potential to change national standards. People with SUD are seeking obstetrical care at every institution and birthing hospital across the country. To take care of this population, and do it well, while reducing healthcare risk and healthcare costs, systems have to get better at providing this kind of all-encompassing treatment. It’s an ongoing transformation.

---

This interview has been edited and condensed for clarity and length.