Opioid Addiction in Pregnancy: More Information about the Use of Methadone Versus Buprenorphine


The MOTHER (Maternal Opioid Treatment: Human Experimental Research) trial of 2012 (Jones et al) gave us much-needed information about how buprenorphine compares to methadone when used to treat opioid-addicted pregnant women. This landmark study showed us buprenorphine can be just as effective as methadone. Babies born to moms on buprenorphine had the same incidence of opioid withdrawal (called neonatal abstinence syndrome, or NAS) at 50%, but the withdrawal was significantly less severe, the babies required about half the medication as the babies born to moms on methadone. Also, buprenorphine-exposed babies spent significantly less time in the hospital – about half as long as methadone-exposed infants.

Some doctors point out that more women on buprenorphine dropped out of that study than women on methadone, and say that proves buprenorphine is less effective. However, the majority of those women didn’t leave treatment; they just left the buprenorphine arm of the study.

This week I read another study, by Meyer et al, soon to be published in the Journal of Addiction Medicine. This study also looked at pregnant patients being treated for opioid addiction.

The authors of this new study pointed out that the MOTHER trial was a placebo- controlled, double- blind study comparing buprenorphine with methadone, but in real life, the decision to start an opioid-addicted pregnant woman on buprenorphine versus methadone is more complex, and determined by other factors. So the study by Meyer et al did a retrospective analysis. They looked at cases where the choice of buprenorphine versus methadone was made by the patient and physician, as happens in real life, then studied the outcomes. The authors of the new study believed findings will be more pertinent to what happens in everyday clinical practice.

In this retrospective cohort study, 609 pregnant patients were started on either buprenorphine (361) or methadone (248). This study took place over the years from 2000 to 2012 at a single site, University of Vermont.

The study collected various data about the newborns: their sex, estimate gestational age at delivery, birth weight, head circumference, length of stay in the hospital, whether the baby received breast milk, and if the child was sent home with the mother. The study also looked at if the newborn has NAS and if the baby needed medication, and length NAS treatment.

In the results, first-time mothers were significantly more likely to start buprenorphine than methadone. Mothers positive for Hepatitis C were more likely to be started on methadone. In both groups, more than 80% of the moms were smokers. About 30% of both groups had to have a C-section at delivery.

Both groups had similar prenatal care; more than 65% of the mother in both groups initiated care within the first trimester. However, women in the buprenorphine group were significantly more likely to get what the authors defined as “adequate” prenatal care. Women on buprenorphine were also more likely to already be in treatment when they became pregnant, compared to the women in the methadone group.

Nineteen women switched from buprenorphine to methadone, out of the three-hundred and sixty-one women who started on buprenorphine. Only five of those patients switched because buprenorphine was not strong enough for them, or other medication side effects. Most were switched to methadone because they needed more intensive monitoring at an opioid treatment program due to continued positive urine drug screens. Only three women out of the three-hundred and sixty-one started on buprenorphine dropped out and were lost from treatment.

No women were switched from methadone to buprenorphine, as one would expect. That’s because in order to switch from a full opioid, methadone, to a partial opioid, buprenorphine, the pregnant opioid addict would have to go into at least mild withdrawal, thus putting her at risk for adverse events. That’s not a risk most doctors are willing to consider.

Babies born to moms on buprenorphine, as compared to methadone, were significantly more likely to have longer gestational age. This is a good thing, because it means there were significantly fewer preterm deliveries on buprenorphine compared to methadone. The babies born to moms on buprenorphine were significantly more likely to have higher birth weights and bigger head circumference.

Just like what we saw in the MOTHER trial, this study also showed that the infants born to moms on buprenorphine required significantly less medication to treat neonatal abstinence syndrome. The buprenorphine-exposed babies required medication for a significantly shorter time than methadone-exposed newborns.

More than 95% of the infants were sent home in the care of the mother or family, which makes me think this study was done on women with fairly good stability at the time of delivery.

The authors of the study concluded that this evidence suggests that buprenorphine gives outcomes that are at least as good as with methadone.

I’d take that conclusion one step farther and say we now have several studies that show less neonatal withdrawal in babies exposed prenatally to buprenorphine compared to methadone. I have to ask myself: knowing what I do from these studies, which medication would I want to take during pregnancy? I’d prefer buprenorphine, and if it didn’t work for any reason, I’d switch to methadone.

I explain all of this to pregnant patients with opioid addiction upon admission, though I’m careful to also point out that methadone is still officially the gold standard in many places.

I think that will change soon. We are getting more information that shows outcomes equal to methadone with less severe neonatal withdrawal.


15 responses to this post.

  1. Posted by nspunx4 on February 28, 2015 at 8:26 pm

    The only thing that worries me is the lack of supervision in early treatment that can happen. Luckily these patients had the option to easily switch to more intensive treatment. I am afraid not every pregnant patient would have that option or take it.

    I would like to see more clinics offer the mono Buprenorphine product in a monitored setting with daily dosing at first. The reason is the combo product is unnecessarily expensive compared to methadone and I don’t beleive the naloxone is an effective deterrent to abuse as I have seen much anecdotal evidence that it is not effective.

    Any thoughts?


    • All of the buprenorphine patients in this study were on the monoproduct, since they were pregnant. Most were prescribed in office-based settings, though they were induced during an inpatient hospitalization, over 24-36 hours. That’s not available in all places.
      I agree with you about daily dosing first. I prescribe to new patients both in an OTP setting, where patients dose daily for the first month or so, and in an office-based setting, where I see patients weekly at first, then the length of time between visits is gradually lengthened. I think patients at the OTP do better, probably because they got much more time and attention from counselors from the very first day. They are certainly retained in treatment better than in my office. I have had a fairly consistent 50% drop out rate in my office, almost all within the first six weeks.


      • Posted by Sandy on July 29, 2015 at 4:25 am

        I was on subutex 8mg bid when I found out I was pregnant after every doctor told me I would never get pregnant. (Pcos) I got down to 0.5mg bid and delivered at 40 weeks on my due date. My baby boy was perfect and had 0 nas and came home day 5 after csection. I was very worried and was unable to really be happy going into labor because I was so scared of what would happen after he was born. I breastfeed and still do now. He never showed and signs of any wd and is a super fat baby, happy and health. My doctor is helping with a study to show that women taking under 1mg qd will have better outcome than ones on low doses of methadone. I love subutex and have 7 years with not one relapse

      • Posted by nspunx4 on July 29, 2015 at 12:10 pm

        Sandy, you TAPERED your Buprenorphine dose during pregnancy? Is that the standard of care? I thought it was the opposite or at least stay on a stable dose.

    • Posted by Boston NAMA on March 7, 2015 at 1:23 am

      The lack of supervision that is the biggest concern needs to be the one that these women who just keep using, I had a women today who was 1 month from her due date in withdrawal and already knowing this baby would not be going home with her when it was born. She did not have the ability to go to a methadone clinic each day but agreed to Subutex treatment. Because it was less intrusive.



  2. Posted by Sharon Dembinski on February 28, 2015 at 8:52 pm

    I can’t help but wonder if the mothers on methadone were as adequately dosed as the buprenorphine mothers. I believe that if moms on methadone and their developing fetuses had adequately covered mu receptors those moms and babies would have similar outcomes as the Buprenorphine cohort did. Under dosing a mother on methadone leaves the mother at risk as well as the baby. Spending 9 month in intrauterine withdrawal, even mild withdrawal can lead to preteen birth, poor weight gain and therefore smaller head circumference as well as more severe NAS. Until we know how adequately he methadone cohort was dosed I don’t believe we can make any valid conclusions from either of these studies.


  3. Methadone is not just officially the gold standard in “many places,” it is still THE gold standard according to the World Health Organization, Institute of Medicine and National Institutes of Health. Is there anywhere it isn’t officially listed as THE gold standard?

    I think it’s important to keep individual studies in perspective. We have individual (or even 2 or 3) studies that can show just about anything… but that’s far different than the MOUND of evidence we have in favor of methadone for pregnant opioid dependent women.

    You may be right that buprenorphine will become another gold standard… but there’s far more things to look at than JUST NAS alone… what about treatment retention (in the real world)? Pregnant or not, methadone’s retention in treatment is FAR superior —- and I would think keeping pregnant women in treatment is FAR more important than the length of time we may need to treat NAS (which is transient and treatable and causes no longterm negative effects on the newborn).

    Zac Talbott
    NAMA Recovery of Tennessee
    National Alliance for Medication Assisted (NAMA) Recovery


    • You may be right. Time and more studies will tell us for sure.


    • Posted by Paul Bowman on March 1, 2015 at 7:38 am

      I really think that so many pregnant methadone patients are not given the education they need to be even knowledge enough to know what to do to have a better outcome for their neonates. None of the women I see even know that they can ask for their dose to be spilt and so many of these women are sick every morning because of improper inadequate doses., no one ever tells them they might need a higher dose.!
      Lastly just a week ago the delivering hospital doctor told this mom absolutely NO breastfeeding because her baby will get dependent again on methadone. I have worked with over 100 moms on methadone and not one was ever given a split dose. Also why are many doctors refusing to use buprenophine without naloxone. Doctors here only use Suboxone.
      Paul Bowman


      • Posted by Paul Bowman on March 1, 2015 at 7:57 am

        The main issue is keeping mother in treatment. Which methadone will be better because it handles cravings in a way that Buprenorphine just does not measure up as well. But time may show that buprenophine pregnancies that are planned births will be much easier on the family with shorter stays and these women appear not to be hard to keep them from being sick from inadequate doses. I’am seeing these babies leave hospital in 10 days or less .
        That is about 1/3 or less the cost to Medicaid or insurance.

  4. Posted by Benjamin K. Phelps on March 4, 2015 at 5:26 pm

    I wanted to point out (forgive me if anybody else already did) that since methadone treatment is not dose-dependent on cost like buprenorphine treatment is, & is still much less expensive, we already have seen that most bupe patients have insurance. This explains quite easily the “adequate” prenatal care they got compared to methadone patients, who are almost ALWAYS paying full price for treatment AND other healthcare out of pocket! And I’d like to re-iterate what Zac said, as well.


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