Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome

Neonatal abstinence syndrome (NAS) is the heartbreaking condition in infants that results from maternal use of opioids during pregnancy. This condition is characterized by infants’ experiences of withdrawal symptoms. Illegal opioid pain relievers or heroin were used by more than 1% of pregnant women in 2011, but illicit drug use is not the only source of opioid use during pregnancy. Surprisingly, opioids were dispensed to over 14% of pregnant women between 2005 and 2011. Approximately 5.8 cases of NAS per 1000 live births occurred by 2012. As the opioid crisis continues and grows in our nation, it is becoming more important to study treatment options available for infants with NAS. The standard treatment is oral methadone and morphine. This study investigates the potential use of buprenorphine in treating NAS.

This retrospective cohort analysis performed in six hospitals in Southwest Ohio between 2012 and 2014 sought to compare the duration of opioid therapy and length of inpatient hospital stay in infants treated for NAS with the standard oral methadone treatment regimen versus sublingual buprenorphine-weaning protocol. At the six sites a total of 163 infants were treated with the standard 8-step methadone protocol, and at one site a total of 38 infants were treated with sublingual buprenorphine based on a 5-step protocol from another study. Buprenorphine dosing was weight-based and initiated at 4.4 μg/kg every 8 hours at a maximum daily dose of 39 μg/kg. Infants who had chronic intrauterine exposure to methadone were excluded from the buprenorphine treatment group and were treated with oral methadone.

The results of the study showed that patients who received buprenorphine had an average duration of treatment of 9.4 days and an average length of stay of 16.3 days while patients who received methadone had an average duration of treatment of 14 days and an average length of stay of 20.7 days. The were no adverse effects or increases in adjunct therapy with phenobarbital in the buprenorphine group compared to the methadone group. Additionally, buprenorphine may be safer than methadone because it has a ceiling effect on respiratory depression.

This study concluded that buprenorphine could be superior to methadone in the treatment of NAS in infants whose mothers did not use methadone. I found this article extremely interesting because I do not often think of the need to treat opioid dependence in infants, and it seems like much more research could be done on this topic. One of the authors of the study was a pharmacist, and I think that this area of practice has a lot of potential for pharmacist involvement. Pharmacists could play in important role in selecting treatment for NAS as well as determining drug dosing because it could be very different for this population and involves constantly changing doses in order to wean infants off of opioids.


J Pediatr. 2016; 170: 39-44.

Tolerance to Long-term Maintenance Methadone Therapy

A study was conducted in patients receiving long-term methadone for opioid maintenance treatment.  It was aimed to study the development of opioid tolerance within these patients.  The study focused on the dose and duration of treatment along with the racemic drugs methadone and levomethadone.  All of the patients displayed DSM IV criteria to receive the treatment for opioid dependence.

The treatment used for a mean of 7.5 years was 370 patients using racemic methadone and 309 using levomethadone.  There was a significant correlation between dosage and duration of treatment.  Only those receiving the treatment for over a year were considered in this study.  The longer the duration of treatment, the larger the dose was.  This is interpreted as a development of tolerance.

Many patients within the study were long-term treatment patients with having up to 30 years of treatment.  There may have been a gradual loss of efficacy of the methadone which would require the increase of dose.  This correlation exists within levomethadone as well.

It was considered that within the past 30 years, the dosing therapy has been changed, and that patients who initially started on the methadone maintenance treatment had initially started with a large dose.  Also, it is taken into consideration that the study is based on self-reported, although anonymous, data which might limit the quality of results.

Overall, the study concluded that there is an increase in tolerance when utilizing long term methadone maintenance therapy in correlation with an increase in dose.  There wasn’t a significant difference between the development of tolerance in patients using methadone or levomethadone.

Although the study may be considered a bit bias, it makes practical sense that an increase in dose would be due to an increase in tolerance.  Is this therapy supposed to be long term?  Shouldn’t the patient be gradually taken off of the treatment?  What can a pharmacist do to intervene with this methadone maintenance treatment?

Gutwinski S, Schoofs N, Stuke H, et al. Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment. Harm Reduction Journal. 2016;13(7).