Posts Tagged ‘buprenorphine during pregnancy’

Pregnant Women with Opioid Use Disorder: Treatment with Combination Buprenorphine/naloxone versus Buprenorphine Monoproduct

 

 

 

 

 

 

 

 

Browsing through my copy of the May/June 2020 issue of the Journal of Addiction Medicine, I started reading an article titled, “Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study.” Then I happened to read the authors’ names and discovered it was written by physicians and scientists from Asheville, NC. I was pleased to see a submission in this major journal by people I knew in my state and read it with interest.

In their introduction, the authors of this article gave some basic facts about opioid use disorder and pregnancy. They quoted statistics from the 2017 NSDUH report, saying 8.5% of pregnant women reported that they had used an illicit substance within the past month, and 1.4% reported the use of some sort of opioid, either heroin or prescription opioid pain medications.

In our nation, opioid use disorder during pregnancy quadrupled between 1999 and 2014, at a rate of 6.5 per 1000 pregnant women. In North Carolina, our rate was 7.8 per 1000 pregnant women. Along with this increased use of opioids, the U.S. has seen a five-fold increase in neonatal abstinence syndrome between 2009 and 2012.

The authors point out that medication (methadone and buprenorphine products) for stabilization of opioid use disorder during pregnancy is the recommended standard of care, endorsed by the World Health Organization, The American College of Obstetrics and Gynecology, the American Society of Addiction Medicine, and the Substance Abuse and Mental Health Services Administration.

Prior to DATA 2000, these pregnant women could only get this treatment at opioid treatment programs, with methadone. Since DATA 2000, these patients also can get treatment with buprenorphine products at office-based practices as well as at opioid treatment programs. All of the patients in this study received buprenorphine product prescriptions from office-based practices, either at the community-based OB/GYN residency program or community-based providers.

Past studies (MOTHER trial, 2010, Jones et al –  another great scientist from North Carolina, at University of North Carolina) showed buprenorphine worked as well as methadone for pregnant patients with opioid use disorders, and over the past ten years, more moms-to-be have chosen buprenorphine over methadone.

This present study was done in order to compare outcomes of moms (and their babies) treated with buprenorphine monoproduct compared to those treated with the combination product, buprenorphine/naloxone.

In the past, pregnant women were usually treated with buprenorphine monoproduct because of fears the fetus could be exposed to naloxone if the combination product was used. However, over the past ten years, more physicians have prescribed the combination product for pregnant women, after some small studies reported no adverse effects. Prescribers were hesitant to prescribe the monoproduct buprenorphine because it is more often misused, and can be injected. The monoproduct has a higher street value than the combination product in most areas, underlining its popularity on the black market.

This retrospective cohort study looked at pregnant patients with opioid use disorder treated from January of 2014 to July 2018. Of the 226 women who met criteria for the study, 108  women taking the buprenorphine monoproduct delivered locally and could be included in the study. Eighty-five women taking the combination product delivered locally and were able to be included in the study.

At the end of the study, the women who had taken the combination product, buprenorphine/naloxone, had outcomes that were not worse than those of the women who had taken the monoproduct. Therefore, this article reassures providers that they can treat pregnant women safely with the combination product.

But hold on…there’s another interesting finding…

The incidence of neonatal abstinence syndrome (NAS) was significantly lower in babies born to moms on the combination product as compared to the monoproduct.

Thirty-five percent of the babies born to moms on the combination product had neonatal abstinence syndrome severe enough to need treatment. However, 55% of babies born to moms on the monoproduct buprenorphine had NAS severe enough to need treatment. That difference was found to be statistically significant.

There were some other differences between the two groups of women that didn’t meet statistical significance, such as age, race, insurance type, presence of chronic pain diagnoses, mental health diagnoses, buprenorphine dose prescribed, and other physical health problems. Interestingly, prescribers working at the residency program were more likely to prescribe the combination buprenorphine/naloxone product than community prescribers.

Intriguing though this finding is, this present study can’t show cause and effect. That is, the most we can say is that the combination buprenorphine is associated with lower neonatal abstinence rates in the babies, but not that the combination buprenorphine product causes lower neonatal abstinence rates. To determine a causal relationship, a different kind of study must be done.

The authors have some ideas about possible factors that could explain these findings. For one thing, there may have been selection bias in which medication was started. This was not the type of study where patients were randomly assigned the monoproduct versus combo product. Selection bias means that perhaps some unknown factor made the study subjects or their prescribers pick one form of medication over the other, and this factor is responsible for the difference in NAS rates.

The authors also suggested that there’s been a trend toward lower NAS rates in recent years compared to earlier years, and that coincided with the trend towards prescribing the combination product instead of the monoproduct. Maybe since both of those things happened at the same same time, it made it appear that the combination product was associated with lower NAS rates.

However, is it possible that the mothers on the combination product actually do absorb more naloxone that we have thought in the past? Is it possible that there’s enough naloxone in those moms’ bloodstream to affect the risk of withdrawal in the newborns?

We know some patients (not necessarily pregnant) complain of low-grade withdrawal symptoms when they take combination products of buprenorphine/naloxone. Some patients report headaches, persistent nausea, and body aches when taking the combination buprenorphine/naloxone sublingual products. These patients’ symptoms resolve on the monoproduct.

Many providers assume such patients are lying, trying to scam them to get monoproduct buprenorphine for some illicit intent. But perhaps sublingual naloxone in the combination product is more active physiologically than we think, causing withdrawal symptoms in susceptible patients, and causing less opioid effect in utero, and reduction of the risk of withdrawal in the newborn.

This issue desperately needs more study, both for pregnant patients with opioid use disorder, and for the patients who describe withdrawal symptoms with the combination product buprenorphine/naloxone.