Posts Tagged ‘buprenorphine for NAS’

New Treatment for Neonatal Abstinence Syndrome

 

 

 

 

 

 

 

 

 

 

The June 15, 2017 issue of the New England Journal of Medicine contained an article of great interest. Written by Kraft et al., this article titled, “Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome,” described a study comparing buprenorphine with morphine solution to treat opioid withdrawal in the newborn. This study showed significantly shorter duration of treatment and shorter median length of hospitalization for babies with neonatal abstinence syndrome when treated with sublingual buprenorphine compared to traditional treatment with morphine oral solution.

This study covers a hot topic. Many people are alarmed at the rising rate of NAS in our nation’s hospitals. The incidence of NAS has risen four-fold from 2003 to 2012, and cost $316 million in care for those babies just in 2012. [1] Any new treatment that can reduce the duration of withdrawal in newborns, and thus reduce treatment costs and parental anxiety, is an exciting new development.

The NEJM study described was done at Thomas Jefferson University in Philadelphia, Pennsylvania, with subjects enrolled from late 2011 until mid-2016. To qualify for the study, the babies had to be born full-term, defined as more than 37 weeks of gestation, and had to have been exposed to opioids during the pregnancy. The infants had to have signs and symptoms of neonatal abstinence syndrome (NAS), and parental consent to participate in the study.

The study, abbreviated BBORN, for “blinded buprenorphine or neonatal morphine solution,” excluded babies with low birth weight, exposure to benzodiazepines within 30 days of delivery, or serious other medical conditions. For the first part of patient enrollment, breast fed babies were excluded, but this restriction was lifted by 2013, with the national trend of that encouraged these mothers to breast feed. Nearly all of the mothers were on methadone maintenance, with doses ranging from 25 to 265 in the group assigned to buprenorphine treatment, and 30-260 in the group assigned to morphine oral solution, regarded as treatment as usual.

The design of this study was very strong, since it was doubly blinded, which means the providers caring for these infants didn’t know which were randomized to buprenorphine and which were randomized to morphine.

This double-blind approach is important in general, but especially important when dealing with the evaluation of babies in withdrawal. Sometimes nurses and other medical professionals who are evaluating withdrawal in babies have an emotional reactions. Some of these people can overestimate the degree of withdrawal, leading to longer hospitalization and over-medication.

If you are wondering “How do they get the babies to keep the medication under their tongue?” I wondered the same thing. The study explained that after getting a buprenorphine dose (or placebo, if their active drug was morphine solution), the babies were given a pacifier to extend the time the medication is in contact with the sublingual mucosa.

How clever. When my cat Yoshi was prescribed buprenorphine for urethritis, I had to dose him with buprenorphine, but there’s no way he kept it under his tongue. I thought some had to have gotten absorbed just from the oral mucosa. He definitely had a response to the medication, being opioid-naïve…he fell asleep, which gave him respite from frantic over-grooming of his urethra…

But I digress.

Anyway, this study showed buprenorphine significant decreased the duration of treatment for NAS, by an average of thirteen days, with no increase in adverse events, as compared to treatment as usual with morphine oral solution. The study authors postulate that the long half-life of buprenorphine levels the peaks and troughs seen with the shorter-acting morphine solution.

The study was limited by its small sample size. The authors wanted to get at least 40 subjects in each treatment arm, but had a hard time recruiting parents willing to enter their newborn into a treatment trial. They ended up with 30 patients in the buprenorphine treatment arm, and 28 in the morphine treatment as usual arm.

I can only imagine how hard it was to convince nervous mothers-to-be to enter their babies in this study. They were likely already worried about NAS in their infants, and perhaps feeling guilty about being pregnant while having the disease of opioid use disorder. Asking a mom – or dad – to then enroll in a study using a new medication (new for this use, at least) would be a hard sell.

Thankfully even with fewer test subjects than desired, the data still reached statistical significance. If future studies can replicate these outcomes, we will have a new medication with which to treat NAS, which will reduce the length of stay in the hospital for babies, reduce medical costs, and get these babies home sooner.

  1. Corr et al., “The Economic Burden of Neonatal Abstinence Syndrome in the United States,” Addiction, 6/13/17 http://onlinelibrary.wiley.com/doi/10.1111/add.13842/abstract
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