Literature Collection

CADTH has previously reviewed the evidence for the use of buprenorphine formulations for the treatment of opioid use disorders (OUDs). One report was limited to pregnant populations, another was a qualitative review of patient preferences and perspectives, and the third was a summary of abstracts based on evidence available in 2017. The objective of the current report is to evaluate the comparative clinical effectiveness, safety, cost-effectiveness and evidencebased guidelines regarding various buprenorphine or combination product of buprenorphine with naloxone (BUP-NAL) formulations for the treatment of OUD.

The purpose of this report is to review and appraise the evidence for the clinical effectiveness, safety, and cost-effectiveness of various buprenorphine monoproducts and buprenorphine-naloxone combination formulations for UOD during pregnancy. Additionally, this report aims to review current evidence-based guidelines regarding appropriate buprenorphine formulation use for this population.

The clinical trial by Kraft et al. provides evidence of a practical alternative pharmacologic approach to the management of the neonatal abstinence syndrome. However, accumulating data show that the appropriate use of nonpharmacologic therapy, especially rooming-in care by parents, results in substantially fewer infants who require opioid therapy to control withdrawal symptoms after exposure to opioids in utero.1-4 In the treatment of withdrawal in infants, the use of the model for treatment in adults, which involves suppression of symptoms with an opiate followed by a tapering reduction in dose, may also need to be challenged. The use of opioid treatment on an as-needed basis3 may prove to be a safer and healthier approach than the use of opioid treatment on a scheduled basis. We strongly advocate that centers caring for infants with the neonatal abstinence syndrome adopt a model of care in which nonpharmacologic treatment is considered to be the primary treatment, with pharmacotherapy secondary. In particular, the facilitation of rooming in and increased parental presence aids in achieving the triple aim of improved quality, improved patient experience, and reduced health care costs.5

Several studies that have focused on deliberate, nonpharmacologic care have shown a reduced need for medications and substantially shorter lengths of stay than the BBORN trial, some as short as 5.9 days.2-4 With small group sizes in this trial, we cannot assume that disparate nonpharmacologic interventions were adequately addressed with randomization, and without controlling for these nonpharmacologic factors it is difficult to interpret the effect of differing pharmacologic therapies. The results of a trial that randomly assigned infants with the neonatal abstinence syndrome to various levels of nonpharmacologic care and that did not control for medication therapy would be similarly difficult to interpret. Nonpharmacologic care has been shown to be an effective therapy for infants with the neonatal abstinence syndrome, and it needs to be treated as such in the literature.

Background  Conventional buprenorphine inductions require patients to abstain from full agonist opioids until they experience mild-to-moderate opioid withdrawal. We described a successful buprenorphine induction case in a pregnant patient using microdosing, which avoided withdrawal symptoms. Case Presentation  The patient is a 29-year-old G2P1001 at 18 2/7 weeks of gestation, who desired a switch from methadone to buprenorphine to minimize neonatal opioid withdrawal syndrome (NOWS), which complicated her last pregnancy. She was given increasing microdoses of buprenorphine over a 7-day period, while continuing her daily dose of methadone. She discontinued the methadone on day 8. She did well during the week of buprenorphine microdosing, with no complaints of withdrawal or cravings. She was engaged in her prenatal care. Her dose of buprenorphine was increased to 8 mg twice daily in the third trimester for some withdrawal symptoms in the evening consisting of new onset nausea and vomiting. The patient underwent an elective 39-week induction of labor and had a spontaneous vaginal delivery of an appropriately grown male fetus. Only nonpharmacologic interventions were used. Conclusion  Buprenorphine microdosing was well tolerated in this patient and avoided withdrawal symptoms in the mothers, and NOWS. A microdosing study in pregnancy is indicated.