Buprenorphine May Best Morphine for Treating NAS

Buprenorphine was associated with a reduction in the length of treatment among infants with neonatal abstinence syndrome compared to other treatments, a systematic review and meta-analysis found.

In a cumulative sample of over 1,000 newborns, sublingual buprenorphine was linked with almost 13 fewer days of treatment compared to morphine (mean difference −12.75 days, 95% CI −17.97 to −7.58), reported Marsha Campbell-Yep, PhD, of the Dalhousie University Faculty of Health School of Nursing in Halifax, Canada, and colleagues.

Compared to morphine, buprenorphine was also associated with a reduction in the length of hospital stay, but there was no statistically significant differences between treatments in the need for adjuvant treatment or in adverse events, the authors wrote in JAMA Pediatrics.

However, they noted that many of the trials involved in the study were at a high risk of bias, and 11 out of 18 did not mask treatments or provide enough information to judge the risk of a blinding bias.

“The incidence of neonatal abstinence syndrome has risen 3 to 5-fold in North America over the past decade and this means more babies are suffering and requiring prolonged hospital stays and treatment,” Campbell-Yep told MedPage Today. “Given the rapid rise in incidence and significant health and financial cost of these babies and families in the healthcare system, we were really surprised at how few clinical trials have been done in this area.”

While neonatal abstinence syndrome has become more prevalent within the past decade, there is currently no standard medication regimen for treating this syndrome, according to Elisha Wachman, MD, of Boston Medical Center, who co-authored an accompanying editorial along with Martha Werler, DSc, of Boston University.

Wachman told MedPage Today separately that nonpharmacologic treatments, like rooming in with parents, can have a significant impact on babies with neonatal abstinence syndrome and should be the first line of approach. When medication is required, morphine is the most commonly administered pharmacologic agent (used in over half of centers) followed by methadone and buprenorphine, she added.

However, there is a wide variation in practice across neonatal units and other centers that may use phenobarbital or opium pharmacologic agents, Campbell-Yep said.

Wachman agreed that this meta-analysis demonstrated buprenorphine was superior to morphine, but noted several limitations.

“It’s hard to combine [these trials] when the treatment protocol is so variable and you’re seeing huge differences even within the same medication,” Wachman told MedPage Today. “With all of this it’s really hard to group them together and make a conclusion because there’s so much unaccounted for and differing across the studies.”

She noted that many of the included studies were not blinded and used a variety of titration and weaning protocols. Some didn’t account for key non-pharmacological factors like rooming in with parents or breastfeeding, which could influence the results as well, she added.

Campbell-Yep told MedPage Today that while the results were robust to bias, they were sensitive to imprecision. She also noted that the majority of studies included in the meta-analysis examining the use of buprenorphine took place at a single site.

Study Details

Researchers examined 18 trials with a mean sample size of 54, where 10 were published after 2000. All trials had a formal treatment protocol except two where it was unclear. Six trials used the Finnegan tool, while four used the modified Finnegan tool to assess symptom severity and guide treatment, but the authors noted that older trials relied on “clinical judgment or informal checklists.”

Eight interventions assessed in 10 studies found that buprenorphine was associated with a reduced length of treatment. Six interventions in seven studies found buprenorphine was also linked with a reduction in the length of hospital stay (-11.43, 95% CI −16.95 to −5.82) compared to morphine.

Compared to clonidine, buprenorphine was also associated with a reduction in the length of treatment of about 2 days (95% CI −16.64 to 12.19) and about a reduction in the length of hospital stay of about 5 days (95% CI −14.15 to 3.53), though the authors noted both of these were based on “indirect evidence only.”

The authors noted numerous limitations to the study, including poor reporting of nonpharmacologic care, a lack of loops of direct and indirect evidence, and an inability to determine the effect of different assessment scales and treatment protocols.

Campbell-Yep told MedPage Today that regardless of the study’s limitations, the results should encourage providers caring for these infants to take pause, evaluate their current practice, and communicate with some of the large-scale networks that frequently treat neonatal abstinence syndrome in order to evaluate which pharmacologic agent might be most appropriate. The study also highlights the need for future clinical trials that compare buprenorphine to other treatments directly, she added.