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‘C-L psychiatrists can confidently recommend buprenorphine/naloxone formulations’
The third-quarter of 2024 Annotations, now on the ACLP website, includes a review by Julian Raffoul, MD, of the comparative safety of in utero exposure to buprenorphine combined with naloxone, versus buprenorphine alone.
Buprenorphine plus naloxone is commonly used to treat opioid use disorders outside of pregnancy. In pregnancy, buprenorphine alone is generally recommended because of limited perinatal safety data on the combination product.
The research reviewed in Annotations, based on US Medicaid-insured beneficiaries from 2000 to 2018, compares perinatal outcomes following both prenatal exposure to buprenorphine with naloxone, and buprenorphine alone.
Outcomes investigated included major congenital malformations, low birth weight, neonatal abstinence syndrome, neonatal intensive care unit admission, preterm birth, respiratory symptoms, small for gestational age, cesarean delivery, and maternal morbidity.
The study identified 3,369 pregnant women exposed to buprenorphine with naloxone during the first trimester (mean age, 28.8 years), and 5,326 exposed to buprenorphine alone or who switched from the combination to buprenorphine alone by the end of the first trimester (mean age, 28.3).
Buprenorphine combined with naloxone (compared with buprenorphine alone) resulted in a lower risk for neonatal abstinence syndrome; and a modestly lower risk for neonatal intensive care unit admission and small for gestational age. Maternal morbidity rates were 2.6% (vs 2.9%). No differences were observed with respect to major congenital malformations overall, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery.
“For the outcomes assessed, compared with buprenorphine alone, buprenorphine with naloxone during pregnancy appears to be a safe treatment option,” say the researchers. “This supports the view that both formulations are reasonable options for the treatment of opioid use disorder in pregnancy, affirming flexibility in collaborative treatment decision-making.”
Dr. Raffoul comments: “The prevalence of opioid use disorder (OUD) in pregnancy increased markedly over the past two decades, reflecting a similar rise in the general population. Several health organizations have consistently recommended the treatment of OUD in pregnancy with methadone or buprenorphine to reduce the illicit use of opioids.
“Buprenorphine has also been shown to be equivalent or superior to methadone for the treatment of OUD. However, limited data exists studying the safety and efficacy of buprenorphine formulated with naloxone in pregnancy, a formulation intended to deter diversion via intranasal or intravenous use.
“Strengths of this study include the use of a large nationwide cohort of Medicaid-insured pregnant women, greatly enhancing the generalizability of the findings, especially to populations most affected by OUD… This study also looked at a broad range of neonatal and maternal outcomes, including neonatal abstinence syndrome, preterm births, NICU admissions, and congenital malformations, providing a comprehensive evaluation of safety. Extensive sensitivity analyses were performed, including high-dimensional propensity scoring and adjusting for prenatal care, which strengthened the validity of the findings.
“However, as with all observational studies, this study is subject to certain limitations inherent in its design. While methods were used to adjust for confounders, unmeasured factors, like severity of OUD, may have influenced the results. Also, some potential confounders such as alcohol use and cigarette smoking may be underreported or missing in the claims data, which could introduce bias.
“The study also relied on prescription fills as a measure of exposure but cannot confirm whether patients actually took the medications as prescribed. And for some rare outcomes, like specific organ system malformations, the sample size was insufficient to draw definitive conclusions as reflected by wide confidence intervals.
“In summary, the study is robust due to its large sample and sophisticated analytical methods, yet inherent limitations do exist simply by its observational nature and due to some gaps in data collection.”
The findings, adds Dr. Raffoul, are nevertheless highly relevant to C-L psychiatrists, particularly those working in health care settings where an addiction consult service is not available and where they may be asked to assist with the treatment of pregnant women with an OUD.
“C-L psychiatrists can confidently recommend buprenorphine/naloxone formulations during pregnancy, knowing that it is associated with similar or better neonatal and maternal outcomes compared to buprenorphine alone. This provides flexibility in treatment options, especially in cases where there is concern about misuse or diversion of buprenorphine. Thus, C-L psychiatrists can play a central role in managing OUD in pregnancy by guiding medication choices while considering patient preferences and risk factors.”